Knee OsteoarthritisPhase 4KOANCT01510457
Milnacipran for Chronic Pain in Knee Osteoarthritis
A Phase 4 study testing Milnacipran in people with Knee Osteoarthritis and Degenerative Joint Disease, run by Dr. Norman Harden.
Trial summary
The patients are asked to take part in this study because you have chronic pain as a result of knee osteoarthritis. This study is done to investigate the pain relieving effects of the study drug Savella (milnacipran HCl) for people who experience chronic osteoarthritis pain. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Knee Osteoarthritis, Degenerative Joint Disease, Chronic Pain
- What is being tested?
- Milnacipran
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 46 participants
- Where
- No sites listed yet
- Study dates
- Nov 2010to Oct 2013
- 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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Knee pain and osteophytes on radiographs OR
- Knee pain plus patient age of 40 years or older, morning stiffness lasting 30 minutes or less, and crepitus (cracking sound) during motion
- Experiences chronic pain for 6 months or longer
- Average pain rating of worse knee is equal to 4 or greater on a 0-10 scale
- If female, is not pregnant or breast feeding, and not currently attempting to conceive; if of childbearing potential, use of a highly effective method of birth control (as determined by Pl)
- Able to walk at least ½ a city block a day, and agrees to try and slowly increase that over the course of study
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- Able to read and speak English and provide informed consent
- Able to understand and comply with all data collection methodology including electronic diary
- Subject agrees to 1) continue their stable drug regimen with no changes during the course of study, 2) only use Tylenol 325 mg of tablets (a maximum of 8 tablets a day) for breakthrough pain, and 3) not use Tylenol or any other pain medicines 12 hours before testing.
Who cannot join
- Subject takes SNRIs (Savella, Cymbalta, Venlafaxine) or other neuroamine re-uptake blockers for mood disorders
- Subject is allergic to SSRIs, SNRIs, or milnacipran
- Subject has severe or untreated psychiatric disturbance (e.g. mania, depression, anxiety, substance dependence)
- Subject is medicated with 'triptans, MAOIs, SSRIs, other SNRIs, tricyclic or heterocyclic antidepressants, lithium, epinephrine, norepinephrine, clonidine or digoxin during the trial
- Subject has a clinical diagnosis of fibromyalgia
- Subject has severe ongoing or unaddressed medical conditions (e.g. Renal or Hepatic disease [creatinine>1.5 ml/dl; AST or ALT> 3x normal limit], uncontrolled hypertension, severe cardiac rate or rhythm disorders, rheumatologic disease (e.g. polymyalgia rheumatica), narrow angle glaucoma, hyponatremia, clotting disorders, uncontrolled seizure disorder or urinary retention)
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- Subject has cardiac implants
- Subject has a knee replacement
- Subject plans to start new pain treatments or therapies during the study (e.g. new pain medication, injections, PT, surgery)
About this study
Official title: Milnacipran for the Pain, Sensory Sensitization and Mood Changes in Knee Osteoarthritis
The patients are asked to take part in this study because you have chronic pain as a result of knee osteoarthritis. This study is done to investigate the pain relieving effects of the study drug Savella (milnacipran HCl) for people who experience chronic osteoarthritis pain. The purpose of this research is to look at how the study drug can be used to benefit people who experience osteoarthritis knee pain. This is a phase IV study done to study the safety and effectiveness of the drug. At this point the drug is already approved by the Food and Drug Administration for people with fibromyalgia but it has not yet been approved for people with knee osteoarthritis.
Read the detailed description
If you are in this study, you will be placed in one of two study groups: one group will receive the study drug and one will receive a placebo. You will be assigned a study group by chance using a process similar to the flip of a coin.
At the first visit (week one) we will review and sign the informed consent, obtain your medical health history, and conduct a brief physical exam. You will also complete several questionnaires about your pain. You will be assessed for your eligibility to participate in this study. If you are eligible, we will conduct some physical and sensory tests and collect a blood sample. The physical tests include a stair climb, 6-minute treadmill test and a 1-minute sit to stand test. The sensory tests allow us to understand your perception of various stimuli such as vibration, light touch, pinprick, heat, cold, hot pain, and cold pain. At the end of the first visit you will be given an electronic diary to record your pain throughout the study. We will also ask you to wear a device in a T-shirt, similar to an accelerometer, that will be used to record your sleep quality and physical activity for 2 days.
At the second (week two) and third visits (week nine) you will be asked to complete the same questionnaires, physical and sensory tests as during the first visit. You will also have to wear the t-shirt with the device for 2 days after each visit.
- Being tested
- Milnacipran, Placebo
- Keywords
- Knee Osteoarthritis, Degenerative Joint Disease, Chronic Pain, Knee Pain
- Medical subject headings
- Osteoarthritis, Knee, Joint Diseases, Chronic Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MilnacipranDrug
Also called Savella (milnacipran HCL) Tablets
Total target dose of 200 mg/day. Subjects will titrate-up according to the following schedule: 25 mg/d (2 pills, 2 days), 50mg mg/d (4 pills, 2 days), 100mg/d (2 pills, 3 days), 150 mg/d (3 pills, 4 days), and steady state is reached once the study participant ingests 200 mg/d(4 pills). The steady state is maintained for 44 days (approx. 6 weeks). If intolerable side effects occur, the dose may be reduced to last tolerable does, a minimum of 100 mg/day at the discretion of the PI. Subjects unable to tolerate 100 mg/day will be discontinued from the study. A 2-week down-titration will be used.
PlaceboDrug
Also called "Sugar Pill"
Subjects will receive identical placebo pills and dosing schedule as that of participants receiving active study medication.
| Study group | Role | What they receive |
|---|---|---|
| Sugar Pill | Placebo comparator | BID placebo Receives: Drug: Placebo |
| Milnacipran | Experimental | Uptitration from 10mg to 50mg BID Milnacipran Receives: Drug: Milnacipran |
What is being measured
The primary outcome is the main question the study is designed to answer.
McGill Pain Questionnaire - Short Form
The MPQ-SF is a well-validated pain measure that permits separation of the sensory and affective components of pain, which are added together to compute a total score. The scale ranges from 0-45 (0=no pain, 45=the most pain).
Measured: Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.
PamSys Actigraph Data
We used a body worn sensor (PAMSys™, Biosensics, LLC, MA)(25-27) embedded in a comfortable t-shirt at the sternal level. Participants wore the PAMSys after the visit for 48 hours. The device provides values related to subjects spontaneous physical activity including percentage of time standing and walking. These variables provide different indexes of participants' level of activity and activity organization, and were reported by subjects with KOA pain as relevant.
Measured: 48 hours after visit 3
Pain Anxiety Symptoms Scale (PASS)
Anxiety scores were collected at least two data points. The Pain Anxiety Symptoms Scale (PASS) is a scale from 0 - 100, where 0 = no anxiety and 100 = the most anxiety.
Measured: Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.
Pain Disability Index (PDI)
The PDI is a seven-item, validated instrument that assesses perceived disability in seven key life areas. It provides a total disability score, and is an indirect measure of self efficacy. The Pain Disability Scale is a scale from 0 - 70, where 0 = no Disability and 70 = the most Disability.
Measured: Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.
Center for Epidemiological Studies Depression Scale CESD-10 (CES-D 10)
The CES-D 10 is a 10-item questionnaire that has been validated for the assessment of depressive symptomatology. The Depression Scale is a scale with a sum score from 0 - 30, where 0 = no Depression and 30 = the most Depression.
Measured: Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.
Pain Visual Analogue Scale
Pain Visual Analogue Scale from 0-100 (0= no pain, and 100= most pain).
Measured: Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.
Secondary outcomes (1)
Daily Diary Entries With Pain, Fatigue and Functioning Scores Three Times a Day
Averages of daily diary outcomes were taken over the first and last week of the trial (week 1 and week 11) to compare pre and post treatment. diary was filled out 3 times a day and asked subjects to rate pain at rest, pain when walking, and fatigue on a scale 0-10 (0=none, and 10=the worst)
Measured: electronic diary entries with pain, fatigue and functioning scores were completed three times a day during week 1 and week 11
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2012 (estimated)
- Study startNov 2010
- Primary completionOct 2013
- Study completionOct 2013
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 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dr. Norman Harden
- Sponsor type
- University, hospital or other
- Collaborators
- Forest Laboratories
- Responsible party
- Sponsor-investigator, Dr. Norman Harden, Shirley Ryan AbilityLab
- Investigators
- Norman Harden, MD, Principal investigator, Center for Pain Studies, Rehabilitation Institute of Chicago
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01510457
- Sponsor's protocol ID
- SAV-MD-23
- Acronym
- KOA
- Status last verified
- May 2015
- First submitted
- 29 Nov 2011
- Last updated
- 22 Jun 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Leaney AA, Lyttle JR, Segan J, Urquhart DM, Cicuttini FM, Chou L, Wluka AE. Antidepressants for hip and knee osteoarthritis. Cochrane Database Syst Rev. 2022 Oct 21;10(10):CD012157. doi: 10.1002/14651858.CD012157.pub2.
PubMed 36269595
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Milnacipran for the Pain, Sensory Sensitization and Mood Changes in Knee Osteoarthritis
- ClinicalTrials.gov ID
- NCT01510457
- Acronym / sponsor ID
- KOA / SAV-MD-23
- Keywords
- Knee Osteoarthritis, Degenerative Joint Disease, Chronic Pain, Knee Pain
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Dr. Norman HardenUniversity, hospital or other
- Collaborators
- Forest Laboratories
- Study start
- Nov 2010
- Primary completion
- Oct 2013 (actual)
- Study completion
- Oct 2013 (actual)
- First posted
- 16 Jan 2012 (estimated)
- Results
- Posted 22 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The patients are asked to take part in this study because you have chronic pain as a result of knee osteoarthritis. This study is done to investigate the pain relieving effects of the study drug Savella (milnacipran HCl) for people who experience chronic osteoarthritis pain. The purpose of this research is to look at how the study drug can be used to benefit people who experience osteoarthritis knee pain. This is a phase IV study done to study the safety and effectiveness of the drug. At this point the drug is already approved by the Food and Drug Administration for people with fibromyalgia but it has not yet been approved for people with knee osteoarthritis.
Detailed description
If you are in this study, you will be placed in one of two study groups: one group will receive the study drug and one will receive a placebo. You will be assigned a study group by chance using a process similar to the flip of a coin.
At the first visit (week one) we will review and sign the informed consent, obtain your medical health history, and conduct a brief physical exam. You will also complete several questionnaires about your pain. You will be assessed for your eligibility to participate in this study. If you are eligible, we will conduct some physical and sensory tests and collect a blood sample. The physical tests include a stair climb, 6-minute treadmill test and a 1-minute sit to stand test. The sensory tests allow us to understand your perception of various stimuli such as vibration, light touch, pinprick, heat, cold, hot pain, and cold pain. At the end of the first visit you will be given an electronic diary to record your pain throughout the study. We will also ask you to wear a device in a T-shirt, similar to an accelerometer, that will be used to record your sleep quality and physical activity for 2 days.
At the second (week two) and third visits (week nine) you will be asked to complete the same questionnaires, physical and sensory tests as during the first visit. You will also have to wear the t-shirt with the device for 2 days after each visit.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sugar Pill | Placebo comparator | Drug: PlaceboBID placebo |
| Milnacipran | Experimental | Drug: MilnacipranUptitration from 10mg to 50mg BID Milnacipran |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Knee pain and osteophytes on radiographs OR
- Knee pain plus patient age of 40 years or older, morning stiffness lasting 30 minutes or less, and crepitus (cracking sound) during motion
- Experiences chronic pain for 6 months or longer
- Average pain rating of worse knee is equal to 4 or greater on a 0-10 scale
- If female, is not pregnant or breast feeding, and not currently attempting to conceive; if of childbearing potential, use of a highly effective method of birth control (as determined by Pl)
Key exclusion criteria (9 listed)
- Subject takes SNRIs (Savella, Cymbalta, Venlafaxine) or other neuroamine re-uptake blockers for mood disorders
- Subject is allergic to SSRIs, SNRIs, or milnacipran
- Subject has severe or untreated psychiatric disturbance (e.g. mania, depression, anxiety, substance dependence)
- Subject is medicated with 'triptans, MAOIs, SSRIs, other SNRIs, tricyclic or heterocyclic antidepressants, lithium, epinephrine, norepinephrine, clonidine or digoxin during the trial
- Subject has a clinical diagnosis of fibromyalgia
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 |
|---|---|---|
| MilnacipranAlso: Savella (milnacipran HCL) TabletsTotal target dose of 200 mg/day. Subjects will titrate-up according to the following schedule: 25 mg/d (2 pills, 2 days), 50mg mg/d (4 pills, 2 days), 100mg/d (2 pills, 3 days), 150 mg/d (3 pills, 4 days), and steady state is reached once the study participant ingests 200 mg/d(4 pills). The steady state is maintained for 44 days (approx. 6 weeks). If intolerable side effects occur, the dose may be reduced to last tolerable does, a minimum of 100 mg/day at the discretion of the PI. Subjects unable to tolerate 100 mg/day will be discontinued from the study. A 2-week down-titration will be used. | Drug | Milnacipran |
| PlaceboAlso: "Sugar Pill"Subjects will receive identical placebo pills and dosing schedule as that of participants receiving active study medication. | Drug | Sugar Pill |
Primary outcome
McGill Pain Questionnaire - Short Form
Time frame: Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.
The MPQ-SF is a well-validated pain measure that permits separation of the sensory and affective components of pain, which are added together to compute a total score. The scale ranges from 0-45 (0=no pain, 45=the most pain).
PamSys Actigraph Data
Time frame: 48 hours after visit 3
We used a body worn sensor (PAMSys™, Biosensics, LLC, MA)(25-27) embedded in a comfortable t-shirt at the sternal level. Participants wore the PAMSys after the visit for 48 hours. The device provides values related to subjects spontaneous physical activity including percentage of time standing and walking. These variables provide different indexes of participants' level of activity and activity organization, and were reported by subjects with KOA pain as relevant.
Pain Anxiety Symptoms Scale (PASS)
Time frame: Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.
Anxiety scores were collected at least two data points. The Pain Anxiety Symptoms Scale (PASS) is a scale from 0 - 100, where 0 = no anxiety and 100 = the most anxiety.
Pain Disability Index (PDI)
Time frame: Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.
The PDI is a seven-item, validated instrument that assesses perceived disability in seven key life areas. It provides a total disability score, and is an indirect measure of self efficacy. The Pain Disability Scale is a scale from 0 - 70, where 0 = no Disability and 70 = the most Disability.
Center for Epidemiological Studies Depression Scale CESD-10 (CES-D 10)
Time frame: Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.
The CES-D 10 is a 10-item questionnaire that has been validated for the assessment of depressive symptomatology. The Depression Scale is a scale with a sum score from 0 - 30, where 0 = no Depression and 30 = the most Depression.
Pain Visual Analogue Scale
Time frame: Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.
Pain Visual Analogue Scale from 0-100 (0= no pain, and 100= most pain).
1 secondary outcome
Daily Diary Entries With Pain, Fatigue and Functioning Scores Three Times a Day
Time frame: electronic diary entries with pain, fatigue and functioning scores were completed three times a day during week 1 and week 11
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 36269595Leaney AA, Lyttle JR, Segan J, Urquhart DM, Cicuttini FM, Chou L, Wluka AE. Antidepressants for hip and knee osteoarthritis. Cochrane Database Syst Rev. 2022 Oct 21;10(10):CD012157. doi: 10.1002/14651858.CD012157.pub2.
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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.
Norman Harden, MD principal investigator
Center for Pain Studies, Rehabilitation Institute of Chicago
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Milnacipran in people with Knee Osteoarthritis and Degenerative Joint Disease, run by Dr. Norman Harden.
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 9 inclusion and 9 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 22 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
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 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 22 Jan 2015). 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?
McGill Pain Questionnaire - Short Form (time frame: Collected at 2 visits over 11 weeks: Visit 1 and Visit 3.). The study lists 6 primary outcomes in all. 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 NCT01510457, 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 22 Jun 2015.