Osteoarthritis, KneePhase 2NCT04224584

A Mechanism Based Proof of Concept Study of the Effects of Duloxetine in the Treatment of Patients With Osteoarthritic Knee Pain

A Phase 2 study testing Duloxetine in people with Osteoarthritis, Knee, run by Kristian Kjær Petersen at 1 site in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Background: Duloxetine provides an analgesic effect of patients with OA. The mode of action of duloxetine is partly believed to act through modulating the descending inhibitory pain pathways from the brainstem towards the spinal cord thereby dampening pain by gating the afferent pain signals from the periphery during… Read more about this study

Who is it for?: Ages 40 to 75 years
Conditions the study is for: Osteoarthritis, Knee
What is being tested?: Duloxetine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 40 participants
Where: 1 siteDenmark
Study dates: 1 Jan 2020to 1 Jul 2021
Phase: Phase 2
Are there results?: None posted in the registry

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 40 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Provide written informed consent and abide by the study restrictions.
Males and females between 40 and 75 years of age and body weight >40 kg and <150 kg with a body mass index (BMI) between 20-35 kg/m2 inclusive
Patients with osteoarthritic knee based on disease diagnostic criteria as presented in section; Inclusion Disease Criteria.
Self-reported pain intensities higher or equal to 5 cm on a 0-10 cm visual analog scale when asked to assess the worst pain within the last 24 hours
Have agreed to maintain the same activity level throughout the course of the study.
Knee pain for at least 14 days per month for the last three months before study entry.

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Osteophytes (with radiographic evidence).
At least 1 of the following 3 conditions: Age >50, or morning stiffness <30 minutes, or crepitus.
Kellgren and Lawrence grade of I, II or III at the index knee. If the patient has had X-rays of the knee joints within the last year, which can confirm the diagnosis, they may be used. Otherwise, a new posterior-anterior view X-ray of both knees will be conducted by CCBR Aalborg.
Worst pain within the last 24-hour must be 5.0cm to 10.0cm (assessed on a 0-10 cm VAS scale anchored at 0cm: no pain and 10cm: worst pain imaginable) prior to enrolment.
Discontinued use of all analgesic medications (including over-the-counter [OTC] analgesics/ Non-Steroidal Anti-Inflammatory Drug (NSAID) at least three days prior to randomization (patients are allowed limited use of analgesic medications).

Who cannot join

Have a history of recurrent seizures other than febrile seizures.
Have a history of frequent and/or severe allergic reactions with multiple medications.
Patients with a current or recent history, as determined by the PI or his delegates, of severe, progressive, and/or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, psychiatric or cerebral disease which could interfere with the patient's participation in the study.
Moderate or great hepatic impairment. Retest of abnormal lab values is allowed once. If still abnormal, the patient will be excluded.
An alanine aminotransaminase (ALAT) higher than the Upper Limit of Normal (ULN) or explain by obesity
Have prior renal transplant, current renal dialysis or severe renal insufficiency (creatinine clearance of <30 mL/min), or serum creatinine laboratory value >1.5 times ULN, based on the reference ranges of the central laboratory.

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Have uncontrolled hypertension (systolic blood pressure over 160 and diastolic blood pressure over 100)
Have active peptic ulcer, gastrointestinal (GI) bleeding or previous unexplained bleeding episodes
Have known inflammatory intestinal disease or gastrointestinal disease which might impact absorption
Patients with congestive heart failure (NYHA II-IV)
Bazett's corrected QT (QTcB) interval > 450 msec for men and > 470 msec for women
Patients with diabetes mellitus and documented atherosclerosis
Patients allergic to the active ingredient of duloxetine or one or more of the excipients
Pregnancy and breast feeding
Non-postmenopausal (defined as the absence of menstruation for at least 12 months and confirmed by assessing the follicle-stimulating hormone (FSH) level) and non-sterile females patients not using fertility control such as either birth control pills, hormonal or copper intrauterine device (IUD), vaginal ring, implant, transdermal release patch, or birth control depot injections
Patients with an active malignancy of any type or a history of malignancy within the last five years (except basal cell carcinoma of the skin that has been excised prior to study start)
Are taking any excluded medications (analgesic medications) that cannot be discontinued during the study period.
Patients in treatment with anticoagulants (with the exception of acetylsalicylic acid)
In treatment with a CYP1A2 inhibitors.
Have received treatment within the last 30 days with a drug that has not received regulatory approval for any indication at Visit 1.
Have a history of substance abuse or dependence within the past year, excluding nicotine and caffeine
Patients at a high risk of infection (e.g. leg ulcers, indwelling urinary catheter and persistent or recurrent chest infections and patients who are permanently bed ridden or wheelchair bound)
Patients with a history of, or suspected, demyelinating disease of the central nervous system (e.g. multiple sclerosis or optic neuritis).
The investigator experiences that the volunteers do not fully understand the experimental pain procedures.
Investigator site personnel directly affiliated with this study and/or their immediate family. Immediate family is defined as a spouse, parent, child, or sibling, whether biological or legally adopted.
Patients on monoamine oxidase inhibitors (MAOIs), dopamine-antagonists, tricyclic antidepressants (TCAs), selective serotonin re-uptake inhibitors (SSRI)s or SNRIs, as well as use of the supplement St. John's Wort
Psychiatric diagnosis or symptoms (e.g. depression or anxiety) that in the opinion of the investigator could interfere with study procedures or participation evaluated using the Mini International Neuropsychiatric Interview (M.I.N.I.).
Has answered "yes" in the Columbia-Suicide Severity Rating Scale (C-SSRS) to suicidal ideation items 4 or 5, or any suicidal behaviour within six months before screening, at screening or at randomization visit, or has been hospitalized or treated for suicidal behaviour in the past five years before screening.
Patients are not allowed to donate blood or blood products during the study
Have secondary causes of arthritis of the knee including septic arthritis, inflammatory joint disease, articular fracture, major dysplasia or congenital abnormality, acromegaly, hemochromatosis, Wilson's disease, and primary osteochondromatosis.
Have had lower extremity surgery (including arthroscopy of the index knee) within 3 months prior to Visit 1 or have surgery planned of the index knee at any time.
Have had significant prior injury to the index knee within 12 months prior to Visit 1.
Use of lower extremity assistive devices other than a cane or knee brace (use of a 'shoe lift' is permitted). Are non-ambulatory or require the use of crutches or a walker. Use of a cane in the hand opposite the index knee is acceptable.
Has had a prior synovial fluid analysis showing a White Blood Cell (WBC) ≥2000mm3 that is indicative of a diagnosis other than OA at the index knee.
Have a confounding painful condition that may interfere with assessment of the index knee. (Knee pain should be the predominant pain. Mild OA of the hands is allowed, for instance).
Have any other musculoskeletal or arthritic condition that may affect the interpretation of the clinical efficacy and/or safety data or otherwise contraindicates participation in this clinical study (i.e., currently symptomatic fractures or any concurrent rheumatic diseases such as but not limited to fibromyalgia, rheumatoid arthritis, gout, pseudo-gout or Paget's disease and Reiter's syndrome are excluded).
Have used corticosteroids prior to baseline:
Intra-articular injection of steroids to the index knee or into any other site than the index knee within the previous three months.
Intra-muscular corticosteroid injections within the previous three months.
Oral corticosteroids within the previous one month.
Have initiated or have changed to an established physiotherapy program within two weeks prior to Visit 2 or during the study period. An established physiotherapy program may be continued throughout the study period if unchanged in frequency and intensity.

Trial locations and contacts

1 site in 1 country.

Denmark1 site

Mech-Sense
Aalborg, 9000

Other trials in Denmark

About this study

Study Rationale: The present study will utilize a set of quantitative pain biomarkers developed to assess peripheral and central manifestations in OA and the influence of duloxetine on those manifestations.

Treatment: Patients will be randomized to one of two treatment sequences:

Sequence 1: 20 mg duloxetine QD for 1 week, 40 mg Duloxetine QD for 1 week, 60 mg duloxetine QD for 10 weeks, 40 mg duloxetine QD for 1 week, 20 mg duloxetine QD for 1 week, followed by 14 weeks of corresponding placebo
Sequence 2: 14 weeks of placebo followed by 20 mg Duloxetine QD for 1 week, 40 mg duloxetine QD for 1 week, 60 mg duloxetine QD for 10 weeks, 40 mg duloxetine QD for 1 week and 20 mg duloxetine QD for 1 week.

The two treatment periods of 14 weeks each are separated by a washout period of two weeks and include a two-week titration period.

Primary Objective: To assess the effect of 60 mg daily maintenance dose administration of Duloxetine for 10 weeks compared with placebo on pain mechanisms.

Sample Size Justification/Statistics: The sample size was calculated to 32 patients providing a power of 85% with a significant level of 0.05 to detect a group difference of 1 point in the change from baseline of the week 12 mean of 24-hour worst pain between duloxetine and placebo treatment.

Patient Selection: Up to 40 patients with osteoarthritic knee pain will be enrolled in this study in order to complete 32 patients.

Study sites:

Mech-Sense Aalborg University Hospital, DK-9000 Aalborg, Denmark Study Assessments: As the primary objective of this study is the assessment of which pain mechanisms are modulated by administration of the study drug, the primary endpoints will be Experimental Mechanism Based Pain Measures (EPMs) including 1) Pressure Pain Thresholds (PPTs), Temporal Summation, Conditioned Pain Modulation (CPM) and Offset Analgesia. In addition, efficacy will be evaluated using 1) pain severity (worst daily pain and night pain), 2) Pittsburgh Sleep Quality Index (PSQI), 3) Brief Pain Inventory (BPI), 4) Investigator and Patient Global Assessment of Changes (IGIC and PGAC), 5) Western Ontario and MacMaster (WOMAC) OA physical function, 6) PainDetect, and 7) Central Sensitization Index (CSI).

Safety: Discontinuation rates and Treatment Emergent Adverse Events (TEAEs). Key Inclusion/Exclusion Criteria: Males or females between 40 and 75 years of age, who are postmenopausal or using allowed contraception methods, and have a Body Mass Index (BMI) between 20-35 kg/m2 inclusive Patient with unilateral or bilateral OA of knee diagnosed according to the American College of Rheumatology (ACR) criteria based on clinical and radiographic evidence with pain severity equal to or higher than 5 on a Visual Analogue Scale (VAS) assessed as the worst pain within the last 24 hours.

Conditions: Osteoarthritis, Knee
Being tested: Duloxetine, Placebo oral tablet
Medical subject headings: Osteoarthritis, Knee

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

DuloxetineDrug
Duloxetine will be administrated with a two weeks up titration followed by a 10 weeks full treatment (60 mg/daily) and finalized by a two weeks discontinuation.
Placebo oral tabletDrug
Placebo will act as a control for duloxetine.

Study groups in NCT04224584
Study group	Role	What they receive
Duloxetine	Active comparator	Duloxetine is a serotonin-norepinephrine reuptake inhibitor. Duloxetine will be administrated as follows: 20 mg/daily duloxetinefor 1 week, 40 mg/daily duloxetine for 1 week, 60 mg/daily duloxetine for 10 weeks, 40 mg/daily duloxetine for 1 week, 20 mg/daily duloxetine for 1 week. Receives: Drug: Duloxetine
Placebo	Placebo comparator	Placebo will be administrated for 14 weeks. Receives: Drug: Placebo oral tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

Pressure Pain Threshold.
Assessment of pressure hyperalgesia. The Pressure Pain Threshold is assessed using a Somedic Handheld algometer (Somedic AB, Sösdala, Sweden). The Pressure Pain Threshold is assessed in kPa (kilo pascal).
Measured: Difference between baseline (prior to treatment) compared with 10 weeks of 60 mg/daily duloxetine compared with placebo

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

1 Jan 20201 Jul 2021

First posted13 Jan 2020
Study start1 Jan 2020
Primary completion1 Jul 2021
Study completion1 Jul 2021

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Osteoarthritis, KneeStudies 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 2
Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind
Who is masked: Participant, Investigator, Outcomes assessor
Enrolment: 40 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04224584
Sponsor's protocol ID: DULKOA2019
Status last verified: Feb 2022
First submitted: 6 Jan 2020
Last updated: 16 Feb 2022
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Undecided

Publications

Ammitzboll N, Arendt-Nielsen L, Bertoli D, Brock C, Olesen AE, Kappel A, Drewes AM, Petersen KK. A mechanism-based proof of concept study on the effects of duloxetine in patients with painful knee osteoarthritis. Trials. 2021 Dec 27;22(1):958. doi: 10.1186/s13063-021-05941-y.
PubMed 34961547

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Osteoarthritis, Knee trials

Study at a glance

From the registry record, last updated by the sponsor on 16 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Mechanism Based Proof of Concept Study of the Effects of Duloxetine in the Treatment of Patients With Osteoarthritic Knee Pain
ClinicalTrials.gov ID: NCT04224584
Acronym / sponsor ID: DULKOA2019
Conditions: Osteoarthritis, Knee
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 40 participants (actual)
Lead sponsor: Kristian Kjær PetersenUniversity, hospital or other
Collaborators: CCBR, Aalborg, Aalborg University Hospital
Study start: 1 Jan 2020 (actual)
Primary completion: 1 Jul 2021 (actual)
Study completion: 1 Jul 2021 (actual)
First posted: 13 Jan 2020 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Treatment: Patients will be randomized to one of two treatment sequences:

Sequence 1: 20 mg duloxetine QD for 1 week, 40 mg Duloxetine QD for 1 week, 60 mg duloxetine QD for 10 weeks, 40 mg duloxetine QD for 1 week, 20 mg duloxetine QD for 1 week, followed by 14 weeks of corresponding placebo
Sequence 2: 14 weeks of placebo followed by 20 mg Duloxetine QD for 1 week, 40 mg duloxetine QD for 1 week, 60 mg duloxetine QD for 10 weeks, 40 mg duloxetine QD for 1 week and 20 mg duloxetine QD for 1 week.

The two treatment periods of 14 weeks each are separated by a washout period of two weeks and include a two-week titration period.

Primary Objective: To assess the effect of 60 mg daily maintenance dose administration of Duloxetine for 10 weeks compared with placebo on pain mechanisms.

Patient Selection: Up to 40 patients with osteoarthritic knee pain will be enrolled in this study in order to complete 32 patients.

Study sites:

Study design

Primary purpose: Basic science
Allocation: Randomised
Intervention model: Crossover
Masking: Triple blind (participant, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Duloxetine	Active comparator	Drug: DuloxetineDuloxetine is a serotonin-norepinephrine reuptake inhibitor. Duloxetine will be administrated as follows: 20 mg/daily duloxetinefor 1 week, 40 mg/daily duloxetine for 1 week, 60 mg/daily duloxetine for 10 weeks, 40 mg/daily duloxetine for 1 week, 20 mg/daily duloxetine for 1 week.
Placebo	Placebo comparator	Drug: Placebo oral tabletPlacebo will be administrated for 14 weeks.

Who may qualify

Ages: 40 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (11 listed)

Provide written informed consent and abide by the study restrictions.
Males and females between 40 and 75 years of age and body weight >40 kg and <150 kg with a body mass index (BMI) between 20-35 kg/m2 inclusive
Patients with osteoarthritic knee based on disease diagnostic criteria as presented in section; Inclusion Disease Criteria.
Self-reported pain intensities higher or equal to 5 cm on a 0-10 cm visual analog scale when asked to assess the worst pain within the last 24 hours
Have agreed to maintain the same activity level throughout the course of the study.

Key exclusion criteria (41 listed)

Have a history of recurrent seizures other than febrile seizures.
Have a history of frequent and/or severe allergic reactions with multiple medications.
Patients with a current or recent history, as determined by the PI or his delegates, of severe, progressive, and/or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, pulmonary, cardiac, neurological, psychiatric or cerebral disease which could interfere with the patient's participation in the study.
Moderate or great hepatic impairment. Retest of abnormal lab values is allowed once. If still abnormal, the patient will be excluded.
An alanine aminotransaminase (ALAT) higher than the Upper Limit of Normal (ULN) or explain by obesity

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
DuloxetineDuloxetine will be administrated with a two weeks up titration followed by a 10 weeks full treatment (60 mg/daily) and finalized by a two weeks discontinuation.	Drug	Duloxetine
Placebo oral tabletPlacebo will act as a control for duloxetine.	Drug	Placebo

Primary outcome

Pressure Pain Threshold.
Time frame: Difference between baseline (prior to treatment) compared with 10 weeks of 60 mg/daily duloxetine compared with placebo
Assessment of pressure hyperalgesia. The Pressure Pain Threshold is assessed using a Somedic Handheld algometer (Somedic AB, Sösdala, Sweden). The Pressure Pain Threshold is assessed in kPa (kilo pascal).

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 Feb 2022.
Derived from this study: PubMed 34961547Ammitzboll N, Arendt-Nielsen L, Bertoli D, Brock C, Olesen AE, Kappel A, Drewes AM, Petersen KK. A mechanism-based proof of concept study on the effects of duloxetine in patients with painful knee osteoarthritis. Trials. 2021 Dec 27;22(1):958. doi: 10.1186/s13063-021-05941-y.
Individual participant dataSharing planned: Undecided

Related trials for Osteoarthritis, Knee

Not yet recruiting
Holistic Healing for Knee Osteoarthritis
Knee Osteoarthritis (Knee OA)
Recruiting
Effect of Anti-inflammatory Diet in Osteoarthritis
Osteoarthritis, Knee
Active, not recruitingPhase 2/3
Single vs Triple Hyaluronic Acid in Knee Osteoarthritis
Osteoarthritis, Knee
Not yet recruiting
The Feasibility of a Virtual/Home-based OA Treatment Program in Older Adults With OA and Multimorbidity
Osteoarthritis of the Knee
RecruitingObservational study
Exploring Factors Linked to Worsening Over Time in People With Early-stage Knee Osteoarthritis and Those With Prior Proven Acute Knee Injury.
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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.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Duloxetine in people with Osteoarthritis, Knee, run by Kristian Kjær Petersen at 1 site in Denmark.

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 11 inclusion and 41 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 16 Feb 2022. 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 Denmark. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Pressure Pain Threshold. (time frame: Difference between baseline (prior to treatment) compared with 10 weeks of 60 mg/daily duloxetine compared with placebo). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04224584, which also lists 1 linked publication.

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 16 Feb 2022.