Knee Pain After Total Knee ArthroplastyPhase 4NCT01780389
Open-label Milnacipran for Persistent Knee Pain One Year After Total Knee Arthroplasty (TKA)
A Phase 4 study testing Open-label flexibly dosed milnacipran in people with Knee Pain After Total Knee Arthroplasty and Osteoarthritis Pain, run by Duke University at 1 site in United States.
Trial summary
The current study examines the effects of milnacipran in patients who have chronic persistent knee pain one year or longer after total knee arthroplasty (TKA) to evaluate for a pain-relieving effect. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Knee Pain After Total Knee Arthroplasty, Osteoarthritis Pain
- What is being tested?
- Open-label flexibly dosed milnacipran
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 5 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2010to Jul 2011
- Phase
- Phase 4
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject is a male or female adult outpatient age 18 or older at the time of consent.
- Subject has chronic persistent pain 1 year after TKA without history of new injury, infection, or implant failure.
- Subject has VAS > or = 40 mm at screen and baseline visits.
- Subject has an understanding, ability and willingness to fully comply with study procedures and restrictions.
- Subject has the ability to provide written, personally signed and dated informed consent to participate in the study, in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 and applicable regulations, before completing any study-related procedures.
Who cannot join
- Subjects unable to complete assessments due to language or cognitive impairment
- Subjects with a history of bipolar disorder or psychosis as confirmed by the Mini International Neuropsychiatric Interview (MINI).
- Subject currently has (or had a history within the last 6 months of) a drug dependence or substance abuse disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision (DSM-IV-TR) criteria (excluding nicotine).
- Subjects who are currently considered a suicide risk, any subject who has previously made a suicide attempt or who has a prior history of or are currently demonstrating active suicidal ideation.
- Subject has any clinically significant ECG or clinically significant laboratory abnormality (including a positive urine drug screen) at Screening.
- Subject has a concurrent chronic or acute illness, disability, or other condition that might confound the results of safety assessments administered in the study or that might increase risk to the subject. Similarly, the subject will be excluded if he or she has any additional condition(s) that in the Investigator's opinion would prohibit the subject from completing the study or would not be in the best interest of the subject. This would include any significant illness or unstable medical condition that could lead to difficulty complying with the protocol.
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- Subjects who do not agree to use adequate and reliable contraception throughout the study.
- Subject previously completed, discontinued or was withdrawn from this study.
- Subject has taken an investigational drug or taken part in a clinical trial within 30 days prior to Screening.
- Subjects treated with antidepressant medication within 4 weeks of screening visit (6 weeks for fluoxetine).
- Subjects with known sensitivity to milnacipran.
- Subjects with liver disease or reduced liver function
- Subjects with obstructive uropathies
- Subjects who consume alcohol in amounts viewed by the Investigator to be contraindicated
- Subjects taking monoamine oxidase inhibitors
- Subjects with uncontrolled narrow angle glaucoma
- Subjects who are pregnant, may become pregnant, or who are nursing
- Subjects with seizure disorders
- Subjects with bleeding disorders or use of other medications that may cause bleeding.
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
The current study examines the effects of milnacipran in patients who have chronic persistent knee pain one year or longer after total knee arthroplasty (TKA) to evaluate for a pain-relieving effect.
Read the detailed description
The current study proposes to collect pilot data on the utility of open-label milnacipran for the treatment of pain and other outcomes in this unfortunate group of patients with chronic persistent pain after TKA. Among marketed serotonin norepinephrine reuptake inhibitors (SNRIs), milnacipran has a unique property in that it blocks serotonin and norepinephrine reuptake equally. It is plausible that equipotent reuptake inhibition may confer greater analgesic benefit compared to other agents, and in preclinical animal models milnacipran has shown superior effects of ameliorating hyperalgesia and allodynia compared to some other antidepressant drugs. Additionally, milnacipran does not have inhibitory effects on cytochrome P (CYP) 450 enzymes, no binding affinity to neurotransmitter receptors liable to cause adverse events, and simple pharmacokinetics.
- Being tested
- Open-label flexibly dosed milnacipran
- Keywords
- Knee, Pain, Osteoarthritis
- Medical subject headings
- Pain, Osteoarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Open-label flexibly dosed milnacipranDrug
Also called Savella
| Study group | Role | What they receive |
|---|---|---|
| Milnacipran | Experimental | Open-label flexibly dosed milnacipran Receives: Drug: Open-label flexibly dosed milnacipran |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Pain Visual Analogue Scale(VAS).
The primary outcome is change in pain VAS from baseline to 12 weeks (baseline score minus 12 week or endpoint score; positive number reflects reduction in pain score). The effect size was calculated using the VAS scores measured on a scale of 0 to 100 mm:
0= absence of pain or no pain noted 100 = worst imaginable pain/as bad as can be The higher the score the greater the over all pain intensity.
Measured: baseline and endpoint 12 weeks
Secondary outcomes (7)
Change in Knee Society Score (KSS).
KSS measures subjective pain and objective function by joint physical exam. This secondary outcome was the change in Knee Society Score(KSS)from baseline through 12 weeks.
KSS scores measured on a scale of 0 to 100 mm:
0 = absence of pain or no pain noted 100= worst imaginable pain/as bad as can be The higher the score the greater the over all pain intensity.
Measured: between baseline and endpoint (12 weeks or early termination)
Global Rating of Change
Measured: Endpoint (12 weeks or early termination)
Change in Total Score of Multidimensional Fatigue Inventory (MFI-20)
Measures subjective fatigue.20-item self-report instrument consisting of five scales: General Fatigue, Physical Fatigue, Reduced Activity, Reduced Motivation, and Mental Fatigue.
Each scale contains four items rated on a scale of one to 5 with the scale score of one having the anchor of entirely true and the scale score of 5 having the anchor of no, not true. The five scales were identified through factor analysis and are assumed to measure different aspects of fatigue. Lowest possible total score = 20 (absent fatigue) Highest possible total score = 100 (maximum fatigue) Total mean cumulative scores were reported
Measured: Baseline to endpoint (12 weeks or early termination)
Change in the Beck Depression Inventory (BDI-II)
The secondary outcome measure is change in Beck Depression Inventory. The scale for this inventory is:
0-9: indicates minimal depression 10-18: indicates mild depression 19-29: indicates moderate depression 30-63: indicates severe depression. The higher the score the degree of depression.
Measured: Baseline to endpoint (12 weeks or early termination)
Change in the Montgomery Asberg Depression Rating Scale
Staff-rated assessment of depressive symptoms. Scale is as follows:
0 to 6 - normal /symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression
Measured: Between baseline and endpoint (12 weeks or early termination)
Change in Total Score of State Trait Anxiety Inventory (STAI)
Assessment of subjective symptoms of current anxiety and chronic anxiety. There are 20 items for assessing trait anxiety and 20 for state anxiety. State anxiety items include: "I am tense; I am worried" and "I feel calm; I feel secure." Trait anxiety items include: "I worry too much over something that really doesn't matter" and "I am content; I am a steady person." All items are rated on a 4-point scale (e.g., from "Almost Never" to "Almost Always"). Higher scores indicate greater anxiety.
Lowest total score is 40 (absent anxiety) Highest total score is 160 (maximum anxiety) Total mean cumulative scores were reported.
Measured: baseline and endpoint (12 weeks or early termination)
Change in Total Score of Short Form-36 (SF-36), Measuring Perceived Quality of Life
Subjective measure of perceived quality of life.The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight.
The eight sections are:
- vitality,
- physical functioning,
- bodily pain,
- general health perceptions,
- physical role functioning,
- emotional role functioning,
- social role functioning,
- mental health
Scale:
0= lowest quality of life 100= high quality of life Higher scores reflect higher quality of life. Total mean cumulative scores were reported.
Measured: baseline and endpoint (12 weeks or early termination)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2013 (estimated)
- Study startOct 2010
- Primary completionJul 2011
- Study completionJul 2011
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Knee Pain After Total Knee ArthroplastyStudies of the same condition, open and under way.
- More trials run by Duke UniversityThe sponsor's other registered studies.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 5 participants (actual)
Sponsor and investigators
- Lead sponsor
- Duke University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Davi M Marks, MD, Principal investigator, Duke University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01780389
- Sponsor's protocol ID
- Pro00017445
- Other IDs
- SAV-MD-08
- Status last verified
- Jan 2015
- First submitted
- 29 Jan 2013
- Last updated
- 6 Feb 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Marks DM, Bolognesi MP. Open-label milnacipran for patients with persistent knee pain 1 year or longer after total knee arthroplasty: a pilot study. Prim Care Companion CNS Disord. 2013;15(4):PCC.12m01496. doi: 10.4088/PCC.12m01496. Epub 2013 Jul 11.
PubMed 24392250
Study at a glance
From the registry record, last updated by the sponsor on 6 Feb 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Open-label Milnacipran for Persistent Knee Pain One Year After Total Knee Arthroplasty (TKA)
- ClinicalTrials.gov ID
- NCT01780389
- Acronym / sponsor ID
- Pro00017445
- Keywords
- Knee, Pain, Osteoarthritis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 5 participants (actual)
- Lead sponsor
- Duke UniversityUniversity, hospital or other
- Study start
- Oct 2010
- Primary completion
- Jul 2011 (actual)
- Study completion
- Jul 2011 (actual)
- First posted
- 31 Jan 2013 (estimated)
- Results
- Posted 23 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The current study examines the effects of milnacipran in patients who have chronic persistent knee pain one year or longer after total knee arthroplasty (TKA) to evaluate for a pain-relieving effect.
Detailed description
The current study proposes to collect pilot data on the utility of open-label milnacipran for the treatment of pain and other outcomes in this unfortunate group of patients with chronic persistent pain after TKA. Among marketed serotonin norepinephrine reuptake inhibitors (SNRIs), milnacipran has a unique property in that it blocks serotonin and norepinephrine reuptake equally. It is plausible that equipotent reuptake inhibition may confer greater analgesic benefit compared to other agents, and in preclinical animal models milnacipran has shown superior effects of ameliorating hyperalgesia and allodynia compared to some other antidepressant drugs. Additionally, milnacipran does not have inhibitory effects on cytochrome P (CYP) 450 enzymes, no binding affinity to neurotransmitter receptors liable to cause adverse events, and simple pharmacokinetics.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Milnacipran | Experimental | Drug: Open-label flexibly dosed milnacipranOpen-label flexibly dosed milnacipran |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Subject is a male or female adult outpatient age 18 or older at the time of consent.
- Subject has chronic persistent pain 1 year after TKA without history of new injury, infection, or implant failure.
- Subject has VAS > or = 40 mm at screen and baseline visits.
- Subject has an understanding, ability and willingness to fully comply with study procedures and restrictions.
- Subject has the ability to provide written, personally signed and dated informed consent to participate in the study, in accordance with the International Conference on Harmonisation (ICH) Good Clinical Practice (GCP) Guideline E6 and applicable regulations, before completing any study-related procedures.
Key exclusion criteria (19 listed)
- Subjects unable to complete assessments due to language or cognitive impairment
- Subjects with a history of bipolar disorder or psychosis as confirmed by the Mini International Neuropsychiatric Interview (MINI).
- Subject currently has (or had a history within the last 6 months of) a drug dependence or substance abuse disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition Text Revision (DSM-IV-TR) criteria (excluding nicotine).
- Subjects who are currently considered a suicide risk, any subject who has previously made a suicide attempt or who has a prior history of or are currently demonstrating active suicidal ideation.
- Subject has any clinically significant ECG or clinically significant laboratory abnormality (including a positive urine drug screen) at Screening.
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 |
|---|---|---|
| Open-label flexibly dosed milnacipranAlso: Savella | Drug | Milnacipran |
Primary outcome
Change in Pain Visual Analogue Scale(VAS).
Time frame: baseline and endpoint 12 weeks
The primary outcome is change in pain VAS from baseline to 12 weeks (baseline score minus 12 week or endpoint score; positive number reflects reduction in pain score). The effect size was calculated using the VAS scores measured on a scale of 0 to 100 mm: 0= absence of pain or no pain noted 100 = worst imaginable pain/as bad as can be The higher the score the greater the over all pain intensity.
7 secondary outcomes
Change in Knee Society Score (KSS).
Time frame: between baseline and endpoint (12 weeks or early termination)
Global Rating of Change
Time frame: Endpoint (12 weeks or early termination)
Change in Total Score of Multidimensional Fatigue Inventory (MFI-20)
Time frame: Baseline to endpoint (12 weeks or early termination)
Change in the Beck Depression Inventory (BDI-II)
Time frame: Baseline to endpoint (12 weeks or early termination)
Change in the Montgomery Asberg Depression Rating Scale
Time frame: Between baseline and endpoint (12 weeks or early termination)
Change in Total Score of State Trait Anxiety Inventory (STAI)
Time frame: baseline and endpoint (12 weeks or early termination)
Change in Total Score of Short Form-36 (SF-36), Measuring Perceived Quality of Life
Time frame: baseline and endpoint (12 weeks or early termination)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Feb 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24392250Marks DM, Bolognesi MP. Open-label milnacipran for patients with persistent knee pain 1 year or longer after total knee arthroplasty: a pilot study. Prim Care Companion CNS Disord. 2013;15(4):PCC.12m01496. doi: 10.4088/PCC.12m01496. Epub 2013 Jul 11.
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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.
Davi M Marks, MD principal investigator
Duke University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Open-label flexibly dosed milnacipran in people with Knee Pain After Total Knee Arthroplasty and Osteoarthritis Pain, run by Duke University at 1 site in United States.
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 5 inclusion and 19 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 6 Feb 2015. 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 United States. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 May 2014). 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?
Change in Pain Visual Analogue Scale(VAS). (time frame: baseline and endpoint 12 weeks). 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 NCT01780389, 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 6 Feb 2015.