Knee OsteoarthritisNCT05014542
Needling Techniques for Knee Osteoarthritis
A study testing Acupuncture and Conventional Medical Treatment in people with Knee Osteoarthritis and Kidney Yin Deficiency, run by Svijetlana Perculija Durdevic at 1 site in Croatia.
Trial summary
The thirty-nine-week open-label clinical study investigates the efficacy of acupuncture for Knee Osteoarthritis (KOA) as adjunctive therapy to analgesics compared to analgesics only and assesses the effects after 9 and 24 weeks, with safety assessment provided. Read more about this study
- Who is it for?
- Ages 50 years and older
- Conditions the study is for
- Knee Osteoarthritis, Kidney Yin Deficiency, Kidney Yang Deficiency
- What is being tested?
- Acupuncture and Conventional Medical Treatment
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 1 siteCroatia
- Study dates
- 2 Jan 2021to 12 Jun 2022
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Clinical diagnosis of Knee Osteoarthritis
- Knee Osteoarthritis for at least 6 months
- painful knee in last month
- radiographic changes of the knee (Kellgren-Lawrence grade 2 or more)
- signed informed consent
- participant can move independently
Who cannot join
- if the participant got knee intra-articular injection 3 months before his entry into the study
- uncontrolled malignant disease
- unstable heart disease
- advanced organ failure disease (NYHA III or IV, or a more than the twofold increase of creatinin, or marked dyspnea)
- unstable psychiatrist's disease
- bleeding diathesis
- anticoagulant use
Trial locations and contacts
1 site in 1 country.
Croatia1 site
Family Medicine Practice Svijetlana Perculija Durdevic, MD
Zagreb, 10000
About this study
Official title: Needling Techniques for Tonifying Kidneys and Dredging Meridians for Knee Osteoarthritis: A Randomized Clinical Trial
The thirty-nine-week open-label clinical study investigates the efficacy of acupuncture for Knee Osteoarthritis (KOA) as adjunctive therapy to analgesics compared to analgesics only and assesses the effects after 9 and 24 weeks, with safety assessment provided.
The study seeks to find possible additional benefits of acupuncture on Kidney Deficiency (KD) while treating KOA with an acupuncture protocol designed to treat KOA following Traditional Chinese Medicine (TCM) theory, which connects KOA with KD as its root cause. The points prescription uses local and Kidney-related points to treat KOA.
Read more
The chronic conditions require a higher number of acupuncture treatments. This study will provide acupuncture treatments in three cycles, each three weeks long, with frequency three times weekly. Twenty-seven acupuncture treatments of KOA during fifteen weeks tend to improve KOA and KDS; symptoms are assessed in 10 successive time points, and treatment effects and effect persistence are analysed.
64 patients with symptomatic KOA are randomly allocated into the Acupuncture (A) or Control (C) group according to their permanent, unique, and coincidental Personal Identification Number, which is randomly given to all citizens in Croatia. Before the experiment starts, demographics and disease parameters of all participants are compared. To objectify acupuncture effects, the enrolled physiatrist's measures included knee measures at 3 time points: baseline, at the end of acupuncture (Week 15), and nine weeks later (Week 24). Subjective evaluations of symptoms are assessed by Western Ontario and McMaster University Arthritis Index (WOMAC) total and subscales scores, Numeric Rating Scale (NRS), and Kidney Deficiency Syndrome Questionnaire (KDSQ) every 3 weeks till the 24th week (9 assessments). Analgesics taken by participants (DRUG) in the last three days before the assessments are recorded. Acupuncture treatment was promised to all participants. Therefore, at Week 25, the between-group analysis ended, and the C group crossed over to receive the identical acupuncture protocol. The 10th assessment in Week 39 was used to estimate, by within-group analysis, the immediate effects of the acupuncture in group C and the effect persistence in group A.
The Lequesne index was introduced additionally at Week 24 as another measure of the knee's functional state.
Read the detailed description
KOA's high prevalence assures the trial's participation motivation of patients regarding associated pain and functional impairment. Besides pain and stiffness, patients experience muscle weakness, poor balance, and joint distortion in an advanced stage. KOA attacks the diseased ones at the age of 50. Pain worsens with joint loading and becomes relieved by rest. KOA supposes bones remodelling, cartilage thinning, synovial thickening, and joint space narrowing. The advanced stage is presented by joint instability, squaring, and even subluxation.
KOA involves both knees and the contributing symptoms of old age from the scope of Kidney deficiency syndromes, such as weakness, insomnia, depression, tinnitus, forgetfulness, feeling cold, hot, low back pain, thirst at night, and disturbed urination could be manifested.
The acupuncture treatment of KOA follows syndrome differentiation. The treatment principle distinguishes the deficient root (primary Kidney deficiency and secondary Blood deficiency) as the cause, and the excessive branch (knee bone Bi syndrome) when in empty Cou Li spaces, the external factor becomes entraped, consequently. An aspiration with treatment is to tonify the Kidney, nourish Qi, tonify and invigorate Blood, remove Damp and Cold by transferring them toward the deficiency rather than expelling, and relieve the channels and collaterals from the obstruction. Moreover, knee meridians should be dredged to improve knee symptoms by a simultaneous reinforcing-reducing technique on local points and reinforcing on KD-related points. Eventually, the improvements of KD indicate better life quality.
The study's design involves two groups: an acupuncture (A) group that receives acupuncture treatment adjunctive to analgesics, and a control (C) group that receives only analgesics. Participants were recruited from the target population of patients over 50 from 2 Family Medicine practices with confirmed KOA. The study sample was formed with inclusion and exclusion criteria. 64 patients were recruited. All medical data of the participants were available to the investigator. After fulfilling the SOAP form (Subjective, Objective, Assessment, Plan) and getting informed written consent, the study sample was randomly allocated into two groups by size of their permanent, unique eleven-digit long Personal Identification Numbers (OIB), which is assigned to all Croatian citizens. Its first ten digits are accidentally chosen, and the last is a control number. Every second participant ordered by the size of OIB belongs to the same group; odd ones belong to the A group, and even ones to the C group. Demographic and disease parameters are compared at baseline to determine if the groups are comparable. All study participants received analgesics and could modify dosages according to their needs. Analgesics were nonsteroidal anti-inflammatory drugs (NSAIDs) and/or tramadol. Taken analgesics were recorded at Weeks 0, 3, 6, 9, 12, 15, 18, 21, 24, and 39. The dose represents an average daily dose of analgesics from the last three days. The dose was recorded after conversion to the comparable dose of the selected representative (ibuprofen), the most prescribed one. The given data will be statistically processed and analyzed.
Patients in the A group started with acupuncture treatment in September 2021, with the first treatment cycle. Each of the 3 treatment cycles, in total, is three weeks long, each consists of 9 treatments, patients will receive acupuncture three times per week and the two adjacent acupuncture cycles are separated by three weeks without acupuncture.
Acupuncture treatment protocol includes local treatment points Dubi (ST-35), Neixiyan (EX-LE-4) and Heding (EX-LE-2), Xuehai (SP-10), Yanglingquan (GB-34), Yinlingquan (SP-9), Zusanli (ST-36), Sanyinjiao (SP-6), and points targeting Kidney deficiency syndrome Taixi (KI-3), Guanyuan (CV 4), and Shenshu (BL-23).
Disposable sterile acupuncture needles 0.30 × 40 mm are used. The depth and angle procedure predicted straight needling on 1-1.5 inches deep, with a mild reinforcing-reducing method for local points, further straight and 0.5-1 inch deep with the reinforcing method for points based on KD syndromes. Complete treatment lasts 30 minutes, and the manipulations are provided every 10 minutes, three times in total.
The sample size was calculated based on the Berman et al. (1999) study. The sample size was calculated by envisioning a two-sided test with unequal variances: type I error 0,05, power 0,95. Group sample sizes of 16 and 16 (i.e. complete study population of 32 subjects) achieve 95,78% power to reject the null hypothesis of equal means and with a significance level (alpha) of 0,050 using a two-sided two-sample unequal-variance t-test.
From a longer treatment period of this study and higher participants' drop-off expected, the population was doubled to 64 subjects in total.
Research methods were determined upon the clinical question "Could the prolonged design of acupuncture treatments on patients with knee osteoarthritis (KOA) decrease pain and improve the function of the knee joints and additionally achieve positive effects on the debilitating symptoms of a Kidney deficiency as a root cause of KOA, measured by recognized questionnaires?".
Evaluation of the therapeutic effects of acupuncture on KOA included WOMAC, VAS, KDSQ scores, and DRUG at Weeks 0, 3, 6, 9, 12, 15, 18, 21, 24, and 39. WOMAC is a renowned questionnaire for KOA evaluation. It measures 5 items for pain, 2 for stiffness, and 17 for functional limitation. VAS is a continuous numeric rating scale of 100 mm in length that is widely used for pain intensity assessment. The KDSQ questionnaire is a valid and reliable measure constructed in 2012 to evaluate Kidney Yin and Yang deficiency syndromes of Hong Kong Chinese middle-aged women by Chen et al. KDSQ represents a valid questionnaire for KD assessment in this study population.
From a total of 10 assessments, the first 9 compared scores between groups A and C. Participants were promised to receive equal acupuncture treatment if they were randomised into the C group. So, group C crossed over to receive the identical protocol from Week 25 to 39, and the 10th assessment was added to both groups of participants to estimate the immediate effects of the acupuncture treatment in the C group and estimate treatment effect persistence in the A group over 24 weeks, in a within-group manner. The physiatrist's assessments at 3 time-points (baseline, 15th Week, and 24th Week) include the standard physiatrist KOA measurements (knee and thigh circumference, range of motion of the knee). The Lequesne index was added as the knee's functional state measure in Week 24.
Data is stored electronically with secured and restricted access. Data transfer will be encrypted, and all data that could identify individuals has been removed.
Study analysis serves to process the effects of acupuncture treatment. Baseline data are obtained before the experiment starts. Besides immediate effects, effects persistence was assessed at Weeks 24 (9 weeks after acupuncture of group A ended) and 39. WOMAC total score at the end of the acupuncture protocol (Week 15) is a primary outcome, while WOMAC subscales, VAS, and KDSQ scores, DRUG at Weeks 15, 24 and 39, and persistence of WOMAC total were secondary and supportive of the primary one. Secondary outcome measures include physiatrists' measures and the Lequesne index as well. Effect sizes are calculated from data comparison to the control group up to Week 24 or baseline at Week 39. Analyses were performed on 64 participants, randomised for the intention-to-treat (ITT) analysis using the maximum available data set (i.e. excluding the missing values) from repeated measures of variables of interest and their variances. ITT analysis, excluding missing values, was selected regarding dropouts that emerged in the study, completely random without any causal clustering. Dropouts produced missing values. Omitting missing values can compromise the statistics and produce bias. Therefore, sensitivity analyses were provided to compare those who dropped out and those who completed the study to determine if data significantly differed. Also, a test calculation with the Last observation carried forward technique (LOCF) with the imputed last observed value in the missing one was performed to check if the obtained effects still stand. All statistical tests are two-sided. The Shapiro-Wilk test tests the normality distribution. The non-parametric Mann-Whitney U test was used for comparability testing with 95% power and α=0,05. The main efficacy indicators tested the comparability of the groups with the Mann-Whitney U test and quantified observed effects by mean differences and Cohen's d.
A participant will be considered to have withdrawn from the trial when consent is revoked or if the participant cannot be contacted or located. Participants will not be withdrawn from the trial for protocol violations. Withdrawal due to an adverse event should be distinguished from withdrawal due to insufficient response.
All adverse events will be recorded in the Adverse Event Report Form at every treatment. If this happens, an adverse event will be followed until its resolution. The serious adverse event must be reported to the Medical Ethics Committee.
It is expected to relieve pain and increase joint mobility, along with alleviating KD and reducing the use of analgesics and confirming the safety of acupuncture.
This is a prospective, interventional, randomized, open-label, controlled trial. It is supported by recent scholarly, peer-reviewed literature. The research method reflects the approach needed to answer the research questions. Research is addressing a gap in the literature that would contribute new findings. The research topic is based on a tangible and cited problem. The research collects and analyses the data, any deviations are documented and approved by NJUCM. The study was designed originally. The acupuncture treatment plan for KOA is designed with the assistance of Professor Xueping Zhou. The study will be conducted in a Family Medicine practice by the experimenter. All financial and operating burdens will be funded from practice resources.
- Being tested
- Acupuncture, Conventional Medical Treatment
- Keywords
- Needling, Techniques, Randomized, Reinforcing, Reducing, Acupuncture
- Medical subject headings
- Osteoarthritis, Knee
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcupunctureProcedure or surgery
Acupuncture treatment includes pricking the skin with acupuncture needles 0.3 x 40 millimetres in size, in the places of prescribed acupuncture points. Placed needles should be manipulated three times, every ten minutes, three times in total. The complete time of treatment is 30 minutes. All treatments will be equal.
Conventional Medical TreatmentDrug
Also called Analgesics
Participants could take their standard conventional medical treatment or analgesics. Analgesics therapy is prescribed by their general practitioner. The dose of analgesics could be modified according to participants' symptoms intensity.
| Study group | Role | What they receive |
|---|---|---|
| Acupuncture Group | Experimental | Participants in Acupuncture group will get acupuncture treatments to their symptomatic knee/knees according to the study protocol. Acupuncture will be provided to participants in three cycles, each three weeks duration, with frequency three times weekly. Period between the cycles is three weeks long. Participants will get acupuncture as adjunctive therapy to conventional medical treatment (analgesic therapy) which dose could vary according to participant symptoms intensity. Participants and investigator are not blinded for treatment type. Receives: Procedure: Acupuncture; Drug: Conventional Medical Treatment |
| Control Group | Active comparator | Participants in Control group will get their standard conventional treatment (analgesics) which dose could vary according to participant symptoms intensity. Participants and investigator are not blinded for treatment type. Receives: Drug: Conventional Medical Treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
WOMAC Total in Week 15
The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) total score is the sum of the three subscales: pain, stiffness, and functional disability.
The minimum value is 0, and the maximum value is 96, where the lower score/value represents a better outcome, and the higher score/value represents a worse outcome.
Measured: Week 15
Secondary outcomes (29)
WOMAC Pain in Week 15
Western Ontario and McMaster University Osteoarthritis (WOMAC) pain subscale, separated from the WOMAC index, evaluates knee OA pain by participants. It comprises 5 questions for pain assessed by a 5-point Likert scale ranging from minimal 0 to maximal 20 points. A bigger score presents a worse outcome, and a lower score relates to a better outcome.
Measured: Week 15
WOMAC Stiffness in Week 15
Western Ontario and McMaster University Osteoarthritis (WOMAC) stiffness subscale, separated from the WOMAC index, and evaluate knee OA stiffness by participants. It comprises 2 questions for stiffness assessed by a 5-point Likert scale between the range from minimal 0 to maximal 8 points. A bigger score presents a worse outcome, and a lower score relates to a better result. WOMAC stiffness measures the stiffness of the knees.
Measured: Week 15
WOMAC Functional Disability in Week 15
Western Ontario and McMaster University Osteoarthritis (WOMAC) functional disability subscale, separated from the WOMAC index, evaluates knee OA functional disability by participants' estimation. It comprises 17 items for functional disability assessment by a 5-point Likert scale ranging from minimal 0 to maximal 68 points. A bigger score presents a worse outcome, and a lower score relates to a better result. WOMAC functional disability measures climbing, rising from a chair/bed, standing, bending, walking, getting in/out of a car/bath/toilet, shopping, putting on socks, sitting and difficulties in domestic duties.
Measured: Week 15
VAS in Week 15
Visual Analogue Scale (VAS) assesses knee OA pain intensity, ranging from 0 to 100; the lower value represents a better outcome, and the higher a worse outcome.
Measured: Week 15
KDSQ in Week 15
The Kidney Deficiency Syndrome Questionnaire (KDSQ) assesses the intensity of Kidney deficiency (KD) symptoms; the minimum value is 0, and the maximum is 69. A lower score/value represents a better outcome, and a higher score/value represents a worse outcome.
This measure represents the effect of acupuncture treatment on KD.
Measured: Week 15
DRUG in Week 15
DRUG is a measure that represents analgesics taken by participants, including various non-steroid anti-inflammatory drugs (NSAIDS) and/or tramadol. Recorded analgesics' doses from the last three days before assessment were recalculated in the comparable dose of the selective representative (ibuprofen) and converted into equivalent dose of milligrams of ibuprofen-ibuprofen equivalent units (IBU). DRUG's units of measure are IBU (units) on the scale ranging from 0 IBU to 4.500 IBU. DRUG decreasement represents a better therapeutic outcome, and an increase in DRUG represents a worse therapeutic outcome. All participants could self-manage the dosage according to their pain.
Measured: Week 15
Active Extension L and R Knees in Week 15
The active extension of the left (L) and right (R) knees in Week 15 is an objective measure taken by an independent physiatrist with a goniometer, expressed on a scale with degrees of a goniometer angle as units.
Knee active extension ranges between 0 and 5 degrees: the higher scores represent knee laxity/instability, and the negative scores represent knee flexion contraction. The higher values represent worse outcomes, and the lower values represent better outcomes.
Measured: Week 15
Active Flexion L and R Knees in Week 15
Active flexion of left (L) and right (R) knees in Week 15 is an objective measure provided by an independent physiatrist with a goniometer, expressed on a scale with degrees of a goniometer angle (units).
Knee active flexion ranges from 0 to a maximum of 135 degrees; the lower score/value represents a worse outcome, and the higher score/value a better one.
Measured: Week 15
Circumference of L and R Upper Leg in Week 15
Circumference of the left (L) and right (R) upper leg in Week 15 is an objective measure, assessed by an independent physiatrist, at the thigh 15 centimetres above the patellar superior margin, measured with a tape measure. The unit of measure is a centimetre (unit) on the measuring tape (scale) with a range from 0 to 100 centimetres. This measure represents a measure of muscular strength or atrophy. Higher values indicate better outcomes from higher muscular volume, and decreased values indicate worse outcomes from weaker muscular volume.
Measured: Week15
Circumference of L and R Knees in Week 15
Circumference of left (L) and right (R) knees at Week 15 is an objective measurement taken by an independent physiatrist; the measure includes the difference in circumference of the knees measured with a tape measure at the middle of the patellae. The unit of measure is a centimetre (unit) on the measuring tape (scale) with a range from 0 to 100 centimetres. This measure represents knee inflammation and joint deformation (abnormal bone growth). Increased values indicate worse outcomes from a higher level of knee inflammation/deformation, and decreased values indicate better outcomes from a lower level of knee inflammation/deformation.
Measured: Week 15
WOMAC Total in Week 24
Western Ontario and McMaster University Osteoarthritis (WOMAC) index's total score is a sum of all three subscales for pain, stiffness, and functional disability, the minimum value is 0, and the maximum value is 96; the lower score/value represents a better outcome, and a higher score/value represents a worse outcome
Measured: Week 24
WOMAC Pain in Week 24
Western Ontario and McMaster University Osteoarthritis (WOMAC) pain subscale, separated from the WOMAC index, evaluates OA pain by participants. It comprises 5 questions for pain assessed by a 5-point Likert scale, ranging from minimal 0 to maximal 20 points. A bigger score presents a worse outcome, and a lower score relates to a better one.
Measured: Week 24
WOMAC Stiffness in Week 24
Western Ontario and McMaster University Osteoarthritis (WOMAC) stiffness subscale, separated from the WOMAC index, evaluates knee OA stiffness by participants. It comprises 2 questions for stiffness assessed by a 5-point Likert scale ranging from minimal 0 to maximal 8 points. A bigger score represents a worse outcome, and a lower score relates to a better result. WOMAC stiffness measures the stiffness of the knees.
Measured: Week 24
WOMAC Functional Disability in Week 24
Western Ontario and McMaster University Osteoarthritis (WOMAC) functional disability subscale, separated from the WOMAC index, evaluates knee OA functional disability by participants' estimation. It comprises 17 items of functional disability assessment by a 5-point Likert scale ranging from minimal 0 to maximal 68 points. A bigger score presents a worse outcome, and a lower score relates to a better result. WOMAC functional disability measures climbing, rising from a chair/bed, standing, bending, walking, getting in/out of a car/bath/toilet, shopping, putting on socks, sitting, and difficulties in domestic duties.
Measured: Week 24
VAS in Week 24
Visual Analogue Scale (VAS) assesses knee OA pain intensity, ranging from 0 to 100; the lower value represents a better outcome, and the higher a worse outcome.
Measured: Week 24
KDSQ in Week 24
The Kidney Deficiency Syndrome Questionnaire (KDSQ) assesses the intensity of kidney deficiency symptoms; the minimum value is 0, and the maximum is 69. A lower score/value represents a better outcome, and a higher score/value represents a worse outcome.
This measure represents the effect of acupuncture treatment on Kidney deficiency (KD).
Measured: Week 24
DRUG in Week 24
DRUG is a measure that represents analgesics taken by participants, including various non-steroid anti-inflammatory drugs (NSAIDS) and/or tramadol. Recorded analgesics' doses from the last three days before assessment were recalculated in the comparable dose of the selective representative (ibuprofen) and converted into equivalent dose of milligrams of ibuprofen-ibuprofen equivalent units (IBU). DRUG's units of measure are IBU (units) on the scale ranging from 0 IBU to 4.500 IBU. DRUG decreasement represents a better therapeutic outcome, and an increase in DRUG represents a worse therapeutic outcome. All participants could self-manage the dosage according to their pain.
Measured: Week 24
Active Extension L and R Knee in Week 24
The active extension of the left (L) and right (R) knees in Week 15 is an objective measure taken by an independent physiatrist with a goniometer, expressed on a scale with degrees of a goniometer angle as units.
Knee active extension ranges between 0 and 5 degrees: the higher scores represent knee laxity/instability, and the negative scores represent knee flexion contraction. The higher values represent worse outcomes, and the lower values represent better outcomes.
Measured: Week 24
Active Flexion L and R Knees in Week 24
Active flexion of left (L) and right (R) knees in Week 15 is an objective measure provided by an independent physiatrist with a goniometer, expressed on a scale with degrees of a goniometer angle (units).
Knee active flexion ranges from 0 to a maximum of 135 degrees; the lower score/value represents a worse outcome, and the higher score/value a better one.
Measured: Week 24
Circumference of L and R Upper Leg in Week 24
Circumference of the left (L) and right (R) upper leg in Week 24 is an objective measure, assessed by an independent physiatrist, at the thigh 15 centimetres above the patellar superior margin, measured with a tape measure. The unit of measure is a centimetre (unit) on the measuring tape (scale) with a range from 0 to 100 centimetres. This measure represents a measure of muscular strength or atrophy. Higher values indicate better outcomes from higher muscular volume, and decreased values indicate worse outcomes from weaker muscular volume.
Measured: Week 24
Circumference of L and R Knee in Week 24
Circumference of the left (L) and right (R) upper leg in Week 24 is an objective measure, assessed by an independent physiatrist, at the thigh 15 centimetres above the patellar superior margin, measured with a tape measure. The unit of measure is a centimetre (unit) on the measuring tape (scale) with a range from 0 to 100 centimetres. This measure represents a measure of muscular strength or atrophy. Higher values indicate better outcomes from higher muscular volume, and decreased values indicate worse outcomes from weaker muscular volume.
Measured: Week 24
WOMAC Total in Week 39
Western Ontario and McMaster University Osteoarthritis (WOMAC) total at the Added assessment at Week 39 in the crossover part compared to pre-experimental baseline value. The total score is a sum of all three subscales: pain, stiffness, and functional limitation. The minimum value is 0, and the maximum value is 96, where the lower score/value represents a better outcome, and a higher score/value represents a worse outcome.
Measured: Week 39
WOMAC Pain in Week 39
The Western Ontario and McMaster University Osteoarthritis (WOMAC) pain subscale, selected from the WOMAC index, evaluates knee OA pain by participants. It comprises 5 questions for pain assessed by a 5-point Likert scale, ranging from minimal 0 to maximal 20 points. A bigger score presents a worse outcome, and a lower score relates to a better one.
Measured: Week 39
WOMAC Stiffness in Week 39
Western Ontario and McMaster University Osteoarthritis (WOMAC) stiffness subscale, separated from the WOMAC index, evaluates knee OA stiffness by participants. It comprises 2 questions for stiffness assessed by a 5-point Likert scale ranging from minimal 0 to maximal 8 points. A bigger score represents a worse outcome, and a lower score relates to a better result. WOMAC stiffness measures the stiffness of the knees.
Measured: Week 39
WOMAC Functional Disability in Week 39
Western Ontario and McMaster University Osteoarthritis (WOMAC) functional disability subscale, separated from the WOMAC index, evaluates knee OA functional disability by participants' estimation. It comprises 17 items for functional disability assessment by a 5-point Likert scale ranging from minimal 0 to maximal 68 points. A bigger score presents a worse outcome, and a lower score relates to a better result. WOMAC functional disability measures climbing, rising from a chair/bed, standing, bending, walking, getting in/out of a car/bath/toilet, shopping, putting on socks, sitting and difficulties in domestic duties.
Measured: Week 39
VAS in Week 39
Visual Analogue Scale (VAS) assesses knee OA pain intensity, ranging from 0 to 100; the lower value represents a better outcome, and the higher a worse outcome.
This measure estimates the treatment effect of acupuncture on knee pain in Week 39 separately for groups A and C.
Measured: Week 39
KDSQ in Week 39
The Kidney Deficiency Syndrome Questionnaire (KDSQ) assesses the intensity of Kidney deficiency symptoms; the minimum value is 0, and the maximum is 69. A lower score/value represents a better outcome, and a higher score/value represents a worse outcome.
This outcome represents the treatment effect of acupuncture on Kidney deficiency symptoms for both groups separately.
Measured: Week 39
DRUG by Added Assessment in Week 39, Crossover Part
DRUG is a measure that represents analgesics taken by participants, including various non-steroid anti-inflammatory drugs (NSAIDS) and/or tramadol. Recorded analgesics' doses from the last three days before assessment were recalculated in the comparable dose of the selective representative (ibuprofen) and converted into equivalent dose of milligrams of ibuprofen-ibuprofen equivalent units (IBU). DRUG's units of measure are IBU (units) on the scale ranging from 0 IBU to 4.500 IBU. DRUG decreasement represents a better therapeutic outcome, and an increase in DRUG represents a worse therapeutic outcome. All participants could self-manage the dosage according to their pain.
Measured: Week 39
Lequesne Index in Week 24, Between-group Analysis
The Lequesne index is an algofunctional index of knee osteoarthritis that comprises three sections. Its score ranges from a minimal 0 (no pain and disability) to 24 (the greatest pain and disability). This index is added to the study in Week 24 as an additional objective measure. It measures pain severity with 5 questions, walking distance with 2 questions, and activities of daily living with 4 questions.
Measured: Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2021
- Study start2 Jan 2021
- Primary completion18 Dec 2021
- Study completion12 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Knee OsteoarthritisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- A randomized, controlled, interventional, prospective.
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 64 participants (actual)
Sponsor and investigators
- Lead sponsor
- Svijetlana Perculija Durdevic
- Sponsor type
- University, hospital or other
- Collaborators
- Nanjing University of Chinese Medicine, Xueping Zhou, Li Ren, University of Zagreb, Health Center Zagreb East, Ljiljana Karadakic
- Responsible party
- Sponsor-investigator, Svijetlana Perculija Durdevic, Family Medicine Practice Svijetlana Perculija Durdevic, MD
- Investigators
- Svijetlana Perculija Durdevic, M.D., Principal investigator, Family Medicine Practice Svijetlana Perculija Durdevic, MD
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05014542
- Sponsor's protocol ID
- 39603233785
- Status last verified
- Jul 2025
- First submitted
- 8 Aug 2021
- Last updated
- 29 Jul 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: IPD that underlies the results reported in this article after deidentification (text, tables, figures, and appendices) for qualified researchers. Approval of the request is a prerequisite to the sharing of data.
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Needling Techniques for Tonifying Kidneys and Dredging Meridians for Knee Osteoarthritis: A Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT05014542
- Acronym / sponsor ID
- 39603233785
- Keywords
- Needling, Techniques, Randomized, Reinforcing, Reducing, Acupuncture
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 64 participants (actual)
- Lead sponsor
- Svijetlana Perculija DurdevicUniversity, hospital or other
- Collaborators
- Nanjing University of Chinese Medicine, Xueping Zhou, Li Ren, University of Zagreb, Health Center Zagreb East, Ljiljana Karadakic
- Study start
- 2 Jan 2021 (actual)
- Primary completion
- 18 Dec 2021 (actual)
- Study completion
- 12 Jun 2022 (actual)
- First posted
- 20 Aug 2021 (actual)
- Results
- Posted 29 Jul 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The thirty-nine-week open-label clinical study investigates the efficacy of acupuncture for Knee Osteoarthritis (KOA) as adjunctive therapy to analgesics compared to analgesics only and assesses the effects after 9 and 24 weeks, with safety assessment provided.
The study seeks to find possible additional benefits of acupuncture on Kidney Deficiency (KD) while treating KOA with an acupuncture protocol designed to treat KOA following Traditional Chinese Medicine (TCM) theory, which connects KOA with KD as its root cause. The points prescription uses local and Kidney-related points to treat KOA.
The chronic conditions require a higher number of acupuncture treatments. This study will provide acupuncture treatments in three cycles, each three weeks long, with frequency three times weekly. Twenty-seven acupuncture treatments of KOA during fifteen weeks tend to improve KOA and KDS; symptoms are assessed in 10 successive time points, and treatment effects and effect persistence are analysed.
64 patients with symptomatic KOA are randomly allocated into the Acupuncture (A) or Control (C) group according to their permanent, unique, and coincidental Personal Identification Number, which is randomly given to all citizens in Croatia. Before the experiment starts, demographics and disease parameters of all participants are compared. To objectify acupuncture effects, the enrolled physiatrist's measures included knee measures at 3 time points: baseline, at the end of acupuncture (Week 15), and nine weeks later (Week 24). Subjective evaluations of symptoms are assessed by Western Ontario and McMaster University Arthritis Index (WOMAC) total and subscales scores, Numeric Rating Scale (NRS), and Kidney Deficiency Syndrome Questionnaire (KDSQ) every 3 weeks till the 24th week (9 assessments). Analgesics taken by participants (DRUG) in the last three days before the assessments are recorded. Acupuncture treatment was promised to all participants. Therefore, at Week 25, the between-group analysis ended, and the C group crossed over to receive the identical acupuncture protocol. The 10th assessment in Week 39 was used to estimate, by within-group analysis, the immediate effects of the acupuncture in group C and the effect persistence in group A.
The Lequesne index was introduced additionally at Week 24 as another measure of the knee's functional state.
Detailed description
KOA's high prevalence assures the trial's participation motivation of patients regarding associated pain and functional impairment. Besides pain and stiffness, patients experience muscle weakness, poor balance, and joint distortion in an advanced stage. KOA attacks the diseased ones at the age of 50. Pain worsens with joint loading and becomes relieved by rest. KOA supposes bones remodelling, cartilage thinning, synovial thickening, and joint space narrowing. The advanced stage is presented by joint instability, squaring, and even subluxation.
KOA involves both knees and the contributing symptoms of old age from the scope of Kidney deficiency syndromes, such as weakness, insomnia, depression, tinnitus, forgetfulness, feeling cold, hot, low back pain, thirst at night, and disturbed urination could be manifested.
The acupuncture treatment of KOA follows syndrome differentiation. The treatment principle distinguishes the deficient root (primary Kidney deficiency and secondary Blood deficiency) as the cause, and the excessive branch (knee bone Bi syndrome) when in empty Cou Li spaces, the external factor becomes entraped, consequently. An aspiration with treatment is to tonify the Kidney, nourish Qi, tonify and invigorate Blood, remove Damp and Cold by transferring them toward the deficiency rather than expelling, and relieve the channels and collaterals from the obstruction. Moreover, knee meridians should be dredged to improve knee symptoms by a simultaneous reinforcing-reducing technique on local points and reinforcing on KD-related points. Eventually, the improvements of KD indicate better life quality.
The study's design involves two groups: an acupuncture (A) group that receives acupuncture treatment adjunctive to analgesics, and a control (C) group that receives only analgesics. Participants were recruited from the target population of patients over 50 from 2 Family Medicine practices with confirmed KOA. The study sample was formed with inclusion and exclusion criteria. 64 patients were recruited. All medical data of the participants were available to the investigator. After fulfilling the SOAP form (Subjective, Objective, Assessment, Plan) and getting informed written consent, the study sample was randomly allocated into two groups by size of their permanent, unique eleven-digit long Personal Identification Numbers (OIB), which is assigned to all Croatian citizens. Its first ten digits are accidentally chosen, and the last is a control number. Every second participant ordered by the size of OIB belongs to the same group; odd ones belong to the A group, and even ones to the C group. Demographic and disease parameters are compared at baseline to determine if the groups are comparable. All study participants received analgesics and could modify dosages according to their needs. Analgesics were nonsteroidal anti-inflammatory drugs (NSAIDs) and/or tramadol. Taken analgesics were recorded at Weeks 0, 3, 6, 9, 12, 15, 18, 21, 24, and 39. The dose represents an average daily dose of analgesics from the last three days. The dose was recorded after conversion to the comparable dose of the selected representative (ibuprofen), the most prescribed one. The given data will be statistically processed and analyzed.
Patients in the A group started with acupuncture treatment in September 2021, with the first treatment cycle. Each of the 3 treatment cycles, in total, is three weeks long, each consists of 9 treatments, patients will receive acupuncture three times per week and the two adjacent acupuncture cycles are separated by three weeks without acupuncture.
Acupuncture treatment protocol includes local treatment points Dubi (ST-35), Neixiyan (EX-LE-4) and Heding (EX-LE-2), Xuehai (SP-10), Yanglingquan (GB-34), Yinlingquan (SP-9), Zusanli (ST-36), Sanyinjiao (SP-6), and points targeting Kidney deficiency syndrome Taixi (KI-3), Guanyuan (CV 4), and Shenshu (BL-23).
Disposable sterile acupuncture needles 0.30 × 40 mm are used. The depth and angle procedure predicted straight needling on 1-1.5 inches deep, with a mild reinforcing-reducing method for local points, further straight and 0.5-1 inch deep with the reinforcing method for points based on KD syndromes. Complete treatment lasts 30 minutes, and the manipulations are provided every 10 minutes, three times in total.
The sample size was calculated based on the Berman et al. (1999) study. The sample size was calculated by envisioning a two-sided test with unequal variances: type I error 0,05, power 0,95. Group sample sizes of 16 and 16 (i.e. complete study population of 32 subjects) achieve 95,78% power to reject the null hypothesis of equal means and with a significance level (alpha) of 0,050 using a two-sided two-sample unequal-variance t-test.
From a longer treatment period of this study and higher participants' drop-off expected, the population was doubled to 64 subjects in total.
Research methods were determined upon the clinical question "Could the prolonged design of acupuncture treatments on patients with knee osteoarthritis (KOA) decrease pain and improve the function of the knee joints and additionally achieve positive effects on the debilitating symptoms of a Kidney deficiency as a root cause of KOA, measured by recognized questionnaires?".
Evaluation of the therapeutic effects of acupuncture on KOA included WOMAC, VAS, KDSQ scores, and DRUG at Weeks 0, 3, 6, 9, 12, 15, 18, 21, 24, and 39. WOMAC is a renowned questionnaire for KOA evaluation. It measures 5 items for pain, 2 for stiffness, and 17 for functional limitation. VAS is a continuous numeric rating scale of 100 mm in length that is widely used for pain intensity assessment. The KDSQ questionnaire is a valid and reliable measure constructed in 2012 to evaluate Kidney Yin and Yang deficiency syndromes of Hong Kong Chinese middle-aged women by Chen et al. KDSQ represents a valid questionnaire for KD assessment in this study population.
From a total of 10 assessments, the first 9 compared scores between groups A and C. Participants were promised to receive equal acupuncture treatment if they were randomised into the C group. So, group C crossed over to receive the identical protocol from Week 25 to 39, and the 10th assessment was added to both groups of participants to estimate the immediate effects of the acupuncture treatment in the C group and estimate treatment effect persistence in the A group over 24 weeks, in a within-group manner. The physiatrist's assessments at 3 time-points (baseline, 15th Week, and 24th Week) include the standard physiatrist KOA measurements (knee and thigh circumference, range of motion of the knee). The Lequesne index was added as the knee's functional state measure in Week 24.
Data is stored electronically with secured and restricted access. Data transfer will be encrypted, and all data that could identify individuals has been removed.
Study analysis serves to process the effects of acupuncture treatment. Baseline data are obtained before the experiment starts. Besides immediate effects, effects persistence was assessed at Weeks 24 (9 weeks after acupuncture of group A ended) and 39. WOMAC total score at the end of the acupuncture protocol (Week 15) is a primary outcome, while WOMAC subscales, VAS, and KDSQ scores, DRUG at Weeks 15, 24 and 39, and persistence of WOMAC total were secondary and supportive of the primary one. Secondary outcome measures include physiatrists' measures and the Lequesne index as well. Effect sizes are calculated from data comparison to the control group up to Week 24 or baseline at Week 39. Analyses were performed on 64 participants, randomised for the intention-to-treat (ITT) analysis using the maximum available data set (i.e. excluding the missing values) from repeated measures of variables of interest and their variances. ITT analysis, excluding missing values, was selected regarding dropouts that emerged in the study, completely random without any causal clustering. Dropouts produced missing values. Omitting missing values can compromise the statistics and produce bias. Therefore, sensitivity analyses were provided to compare those who dropped out and those who completed the study to determine if data significantly differed. Also, a test calculation with the Last observation carried forward technique (LOCF) with the imputed last observed value in the missing one was performed to check if the obtained effects still stand. All statistical tests are two-sided. The Shapiro-Wilk test tests the normality distribution. The non-parametric Mann-Whitney U test was used for comparability testing with 95% power and α=0,05. The main efficacy indicators tested the comparability of the groups with the Mann-Whitney U test and quantified observed effects by mean differences and Cohen's d.
A participant will be considered to have withdrawn from the trial when consent is revoked or if the participant cannot be contacted or located. Participants will not be withdrawn from the trial for protocol violations. Withdrawal due to an adverse event should be distinguished from withdrawal due to insufficient response.
All adverse events will be recorded in the Adverse Event Report Form at every treatment. If this happens, an adverse event will be followed until its resolution. The serious adverse event must be reported to the Medical Ethics Committee.
It is expected to relieve pain and increase joint mobility, along with alleviating KD and reducing the use of analgesics and confirming the safety of acupuncture.
This is a prospective, interventional, randomized, open-label, controlled trial. It is supported by recent scholarly, peer-reviewed literature. The research method reflects the approach needed to answer the research questions. Research is addressing a gap in the literature that would contribute new findings. The research topic is based on a tangible and cited problem. The research collects and analyses the data, any deviations are documented and approved by NJUCM. The study was designed originally. The acupuncture treatment plan for KOA is designed with the assistance of Professor Xueping Zhou. The study will be conducted in a Family Medicine practice by the experimenter. All financial and operating burdens will be funded from practice resources.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- A randomized, controlled, interventional, prospective.
| Arm | Type | Receives |
|---|---|---|
| Acupuncture Group | Experimental | Procedure: Acupuncture, Drug: Conventional Medical TreatmentParticipants in Acupuncture group will get acupuncture treatments to their symptomatic knee/knees according to the study protocol. Acupuncture will be provided to participants in three cycles, each three weeks duration, with frequency three times weekly. Period between the cycles is three weeks long. Participants will get acupuncture as adjunctive therapy to conventional medical treatment (analgesic therapy) which dose could vary according to participant symptoms intensity. Participants and investigator are not blinded for treatment type. |
| Control Group | Active comparator | Drug: Conventional Medical TreatmentParticipants in Control group will get their standard conventional treatment (analgesics) which dose could vary according to participant symptoms intensity. Participants and investigator are not blinded for treatment type. |
Who may qualify
- Ages
- 50 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Clinical diagnosis of Knee Osteoarthritis
- Knee Osteoarthritis for at least 6 months
- painful knee in last month
- radiographic changes of the knee (Kellgren-Lawrence grade 2 or more)
- signed informed consent
Key exclusion criteria (7 listed)
- if the participant got knee intra-articular injection 3 months before his entry into the study
- uncontrolled malignant disease
- unstable heart disease
- advanced organ failure disease (NYHA III or IV, or a more than the twofold increase of creatinin, or marked dyspnea)
- unstable psychiatrist's disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AcupunctureAcupuncture treatment includes pricking the skin with acupuncture needles 0.3 x 40 millimetres in size, in the places of prescribed acupuncture points. Placed needles should be manipulated three times, every ten minutes, three times in total. The complete time of treatment is 30 minutes. All treatments will be equal. | Procedure or surgery | Acupuncture Group |
| Conventional Medical TreatmentAlso: AnalgesicsParticipants could take their standard conventional medical treatment or analgesics. Analgesics therapy is prescribed by their general practitioner. The dose of analgesics could be modified according to participants' symptoms intensity. | Drug | Acupuncture Group, Control Group |
Primary outcome
WOMAC Total in Week 15
Time frame: Week 15
The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) total score is the sum of the three subscales: pain, stiffness, and functional disability. The minimum value is 0, and the maximum value is 96, where the lower score/value represents a better outcome, and the higher score/value represents a worse outcome.
29 secondary outcomes
WOMAC Pain in Week 15
Time frame: Week 15
WOMAC Stiffness in Week 15
Time frame: Week 15
WOMAC Functional Disability in Week 15
Time frame: Week 15
VAS in Week 15
Time frame: Week 15
KDSQ in Week 15
Time frame: Week 15
DRUG in Week 15
Time frame: Week 15
Active Extension L and R Knees in Week 15
Time frame: Week 15
Active Flexion L and R Knees in Week 15
Time frame: Week 15
Circumference of L and R Upper Leg in Week 15
Time frame: Week15
Circumference of L and R Knees in Week 15
Time frame: Week 15
WOMAC Total in Week 24
Time frame: Week 24
WOMAC Pain in Week 24
Time frame: Week 24
WOMAC Stiffness in Week 24
Time frame: Week 24
WOMAC Functional Disability in Week 24
Time frame: Week 24
VAS in Week 24
Time frame: Week 24
KDSQ in Week 24
Time frame: Week 24
DRUG in Week 24
Time frame: Week 24
Active Extension L and R Knee in Week 24
Time frame: Week 24
Active Flexion L and R Knees in Week 24
Time frame: Week 24
Circumference of L and R Upper Leg in Week 24
Time frame: Week 24
Circumference of L and R Knee in Week 24
Time frame: Week 24
WOMAC Total in Week 39
Time frame: Week 39
WOMAC Pain in Week 39
Time frame: Week 39
WOMAC Stiffness in Week 39
Time frame: Week 39
WOMAC Functional Disability in Week 39
Time frame: Week 39
VAS in Week 39
Time frame: Week 39
KDSQ in Week 39
Time frame: Week 39
DRUG by Added Assessment in Week 39, Crossover Part
Time frame: Week 39
Lequesne Index in Week 24, Between-group Analysis
Time frame: Week 24
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. IPD that underlies the results reported in this article after deidentification (text, tables, figures, and appendices) for qualified researchers. Approval of the request is a prerequisite to the sharing of data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Svijetlana Perculija Durdevic, M.D. principal investigator
Family Medicine Practice Svijetlana Perculija Durdevic, MD
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Acupuncture and Conventional Medical Treatment in people with Knee Osteoarthritis and Kidney Yin Deficiency, run by Svijetlana Perculija Durdevic at 1 site in Croatia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Croatia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Jul 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
WOMAC Total in Week 15 (time frame: Week 15). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jul 2025.