Multiple SclerosisPhase 2/3NCT00457730
A Study to Test the Use of Duloxetine for Pain in MS
A Phase 2/3 study testing Duloxetine in people with Multiple Sclerosis, run by Brown, Theodore R., M.D., MPH at 1 site in United States.
Trial summary
Many patients with Multiple Sclerosis experience pain that is caused by the effects of MS on the nervous system. The purpose of this study is to see if an investigational drug (Duloxetine) will reduce pain in subjects with MS. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Duloxetine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2007to Aug 2012
- Phase
- Phase 2/3
- 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
- Diagnosis of MS made at least 3 months prior based on McDonald or Proser criteria.
- Age over 17.
- Clinical stability defined as no MS exacerbation or change in disease modifying therapy for 90 days prior to screening.
- Daily pain attributed to MS, present for a minimum of 2 months prior to screening.
- Minimum baseline score of 4 on the 24-h Worst Pain Score rated on an 11 point (0-10) point Likert Scale within the identified region of central pain.
Who cannot join
- Pain that could not clearly be differentiated from causes other than Multiple Sclerosis, such as diabetic neuropathy, PVD, arthritis or other musculoskeletal condition, chronic headache, visceral pain.
- Transient pains such as dysesthetic L'Hermittes sign alone.
- Current or historical diagnosis of mania, bipolar disorder or psychosis.
- Concomitant use of monoamine oxidase inhibitors (MAOI) or thioridazine.(MAOI drug must be discontinued 14 days prior to enrollment. At least 5 days must have passed after study drug discontinuation before MAOI drug may be started.)
- Concomitant use of a serotonin reuptake inhibitor or venlafaxine or duloxetine within 4 weeks of baseline.
- Use of any analgesic medication except ibuprofen for neurogenic pain 7 days prior to the baseline visit and until study termination.
Show all 18Show fewer
- Use of an opioid, marijuana or dronabinol within 7 days of baseline.
- Narrow angle glaucoma.
- Depression with suicidality.
- Substantial alcohol use. Because it is possible that Duloxetine and alcohol interact to cause liver injury, duloxetine should not be prescribed to patients with substantial alcohol use. Potential subjects will be asked how much alcohol they drink. If the answer is over 2 drinks a day this will generally constitute an exclusion.
- History of chronic hepatic insufficiency or ALT or AST> twice the upper limit of normal. Because it is possible thast Duloxetine may aggravate pre exisitng liver disease, duloxetine should not be prescribed to patients with chronic liver disease.
- Renal insufficiency (Creatinine Clearance , 30mL/minor serum creatinine > 1.9). Duloxetine is not recommended for patients with end stage renal disease (requiring dialysis) or severe renal impairment. Population PK analyses suggest that mild to moderate degrees of renal dysfunction (estimated CrCl 30-80ml/min)have no significant effect on Duloxetine clearance. We will calculate creatinine clearance using the Cockcroft-Gault calculation. This is the most common calculation used in FDA producy labeling: Males=(140-age)(wt in kg)(serum creatinine)(72). Females= malesx 0.85.
- Uncontrolled hypertention (SBP>180, DBP>105)
- Females who are breast feeding, pregnant, or have potential to become pregnant during the course of the study.(fertile and unwilling/unable to use effective contraceptive measures)
- Any other serious and/or unstable medical condition.
- Allergy to ibuprofen or any other non steroidal anti inflammatory drug (NSAID)
- Any history of peptic ulcer disease within 2 years or lifetime history of NSAID-associated gastritis or other toxicity.
- Patients taking low dose aspirin will be instructed to contact their primary physicianto ask whether they may safely discontinue aspirin while participating in this study. If the recommendation is to continue aspirin or if use of aspirin is for secondary prevention of arteriosclerotic disease, then they will be excluded.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Randomized Placebo Controlled Trial of Duloxetine for Central Pain in Multiple Sclerosis
Many patients with Multiple Sclerosis experience pain that is caused by the effects of MS on the nervous system.
The purpose of this study is to see if an investigational drug (Duloxetine) will reduce pain in subjects with MS.
Read more
The US Food and Drug administration (FDA) has approved this drug for use with depression or pain from diabetes.However, it is considered investigational for this study because it has not been approved for patients with MS.
This study will recruit patients with MS who have central pain which is 4 or greater on a scale of 1-10. Patients must have experienced pain for 2 months or longer prior to begining the study.The study will last 10 weeks, patients will be randomized either Duloxetine or placebo and will be carefully monitored throughout the study. Patients will keep pain/sleep diaries during the study period and will be provided Ibuprofen for pain control.
Read the detailed description
Between 350,000 and 400,000 Americans have Multiple Sclerosis, a chronic neurological disease characterized by demyelination and axonal degeneration. Pain is an important symptom of MS, reported in 44% to 80% of patients.
Duloxetine is FDA apprBetween 350,000 and 400,000 Americans have Multiple Sclerosis, a chronic neurological disease characterized by demyelination and axonal degeneration. Pain is an important symptom of MS, reported in 44% to 80% of patients.
Duloxetine is FDA approved for use in treatment of diabetic painful neuropathy and depression. Since the analgesic mechanism of action of Duloxetine is believed to occur in the Central Nervous System, there is reason to believe that it may also be effective in central pain conditions, such as MS.
Our study design includes a 1:1 randomization of Duloxetine to placebo. We hypothesize that the Duloxetine group will experience reductions in the weekly 24 hour average and worst pain scores that exceed 1.5 and that are significantly greater than reductions achieved in the placebo group. We also hypothesize that Duloxetine will be well tolerated with no significant group differences in adverse effects, sleep and quality of life as measured by the SF-36 approved for use in treatment of diabetic painful neuropathy and depression. Since the analgesic mechanism of action of Duloxetine is believed to occur in the Central Nervous System, there is reason to believe that it may also be effective in central pain conditions, such as MS.
Our study design includes a 1:1 randomization of Duloxetine to placebo. We hypothesize that the Duloxetine group will experience reductions in the weekly 24 hour average and worst pain scores that exceed 1.5 and that are significantly greater than reductions achieved in the placebo group. We also hypothesize that Duloxetine will be well tolerated with no significant group differences in adverse effects, sleep and quality of life as measured by the SF-36.
- Conditions
- Multiple Sclerosis
- Being tested
- Duloxetine, Placebo
- Keywords
- Multiple Sclerosis, Duloxetine, Pain
- Medical subject headings
- Multiple Sclerosis, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DuloxetineDrug
Also called Cymbalta
Patients will be randomly assigned to Duloxetine 30mg/d for 1 week, 60mg/d for 5 weeks and 30mg/d for 1 week or placebo for 7 weeks under double-blind conditions.
PlaceboDrug
Also called Sugar Pill
Subjects are randomized to either Duloxetine or Placebo
| Study group | Role | What they receive |
|---|---|---|
| Duloxetine | Experimental | subjects will be randomized to study drug (Duloxetine) or Placebo. Subjects will take 30 mg (10 capsules) titrate up to 60 mg( 40 capsules) and titrate back down to 30 mg. Receives: Drug: Duloxetine |
| placebo | Placebo comparator | matched placebo medication Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Worst Pain Score
Weekly mean of 24 hour Worst Pain Score, percent change from baseline. Range is 0-10 with 0= no pain and 10= worst possible pain.
Measured: at week 6
Secondary outcomes (2)
Percent Change in Average Pain Score.
Percent change in Weekly mean of 24 hour Average pain Score, Week 6 vs. baseline. Range is 0-10 with 0= no pain and 10= worst possible pain.
Measured: at week 6
Global Impression of Change
global impression: "How do you feel about the effects of the medication over the past 7 days? 7 point scale, 7 = delighted, 1= terrible
Measured: Week 6 vs baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Apr 2007 (estimated)
- Study startJan 2007
- Primary completionAug 2012
- Study completionAug 2012
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 Multiple SclerosisStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Care provider, Investigator
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brown, Theodore R., M.D., MPH
- Collaborators
- Eli Lilly and Company
- Responsible party
- Principal investigator, Theodore R Brown, Brown, Theodore R., M.D., MPH
- Investigators
- Theodore R Brown, MD.MPH, Principal investigator, Evergreen Healthcare
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00457730
- Sponsor's protocol ID
- 1083575
- Other IDs
- WIRB Protocol Number: 20061712
- Status last verified
- Apr 2015
- First submitted
- 4 Apr 2007
- Last updated
- 27 Apr 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Placebo Controlled Trial of Duloxetine for Central Pain in Multiple Sclerosis
- ClinicalTrials.gov ID
- NCT00457730
- Acronym / sponsor ID
- 1083575
- Conditions
- Multiple Sclerosis
- Keywords
- Multiple Sclerosis, Duloxetine, Pain
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Brown, Theodore R., M.D., MPH
- Collaborators
- Eli Lilly and Company
- Study start
- Jan 2007
- Primary completion
- Aug 2012 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 6 Apr 2007 (estimated)
- Results
- Posted 6 Apr 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Many patients with Multiple Sclerosis experience pain that is caused by the effects of MS on the nervous system.
The purpose of this study is to see if an investigational drug (Duloxetine) will reduce pain in subjects with MS.
The US Food and Drug administration (FDA) has approved this drug for use with depression or pain from diabetes.However, it is considered investigational for this study because it has not been approved for patients with MS.
This study will recruit patients with MS who have central pain which is 4 or greater on a scale of 1-10. Patients must have experienced pain for 2 months or longer prior to begining the study.The study will last 10 weeks, patients will be randomized either Duloxetine or placebo and will be carefully monitored throughout the study. Patients will keep pain/sleep diaries during the study period and will be provided Ibuprofen for pain control.
Detailed description
Between 350,000 and 400,000 Americans have Multiple Sclerosis, a chronic neurological disease characterized by demyelination and axonal degeneration. Pain is an important symptom of MS, reported in 44% to 80% of patients.
Duloxetine is FDA apprBetween 350,000 and 400,000 Americans have Multiple Sclerosis, a chronic neurological disease characterized by demyelination and axonal degeneration. Pain is an important symptom of MS, reported in 44% to 80% of patients.
Duloxetine is FDA approved for use in treatment of diabetic painful neuropathy and depression. Since the analgesic mechanism of action of Duloxetine is believed to occur in the Central Nervous System, there is reason to believe that it may also be effective in central pain conditions, such as MS.
Our study design includes a 1:1 randomization of Duloxetine to placebo. We hypothesize that the Duloxetine group will experience reductions in the weekly 24 hour average and worst pain scores that exceed 1.5 and that are significantly greater than reductions achieved in the placebo group. We also hypothesize that Duloxetine will be well tolerated with no significant group differences in adverse effects, sleep and quality of life as measured by the SF-36 approved for use in treatment of diabetic painful neuropathy and depression. Since the analgesic mechanism of action of Duloxetine is believed to occur in the Central Nervous System, there is reason to believe that it may also be effective in central pain conditions, such as MS.
Our study design includes a 1:1 randomization of Duloxetine to placebo. We hypothesize that the Duloxetine group will experience reductions in the weekly 24 hour average and worst pain scores that exceed 1.5 and that are significantly greater than reductions achieved in the placebo group. We also hypothesize that Duloxetine will be well tolerated with no significant group differences in adverse effects, sleep and quality of life as measured by the SF-36.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Duloxetine | Experimental | Drug: Duloxetinesubjects will be randomized to study drug (Duloxetine) or Placebo. Subjects will take 30 mg (10 capsules) titrate up to 60 mg( 40 capsules) and titrate back down to 30 mg. |
| placebo | Placebo comparator | Drug: Placebomatched placebo medication |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosis of MS made at least 3 months prior based on McDonald or Proser criteria.
- Age over 17.
- Clinical stability defined as no MS exacerbation or change in disease modifying therapy for 90 days prior to screening.
- Daily pain attributed to MS, present for a minimum of 2 months prior to screening.
- Minimum baseline score of 4 on the 24-h Worst Pain Score rated on an 11 point (0-10) point Likert Scale within the identified region of central pain.
Key exclusion criteria (18 listed)
- Pain that could not clearly be differentiated from causes other than Multiple Sclerosis, such as diabetic neuropathy, PVD, arthritis or other musculoskeletal condition, chronic headache, visceral pain.
- Transient pains such as dysesthetic L'Hermittes sign alone.
- Current or historical diagnosis of mania, bipolar disorder or psychosis.
- Concomitant use of monoamine oxidase inhibitors (MAOI) or thioridazine.(MAOI drug must be discontinued 14 days prior to enrollment. At least 5 days must have passed after study drug discontinuation before MAOI drug may be started.)
- Concomitant use of a serotonin reuptake inhibitor or venlafaxine or duloxetine within 4 weeks of baseline.
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 |
|---|---|---|
| DuloxetineAlso: CymbaltaPatients will be randomly assigned to Duloxetine 30mg/d for 1 week, 60mg/d for 5 weeks and 30mg/d for 1 week or placebo for 7 weeks under double-blind conditions. | Drug | Duloxetine |
| PlaceboAlso: Sugar PillSubjects are randomized to either Duloxetine or Placebo | Drug | placebo |
Primary outcome
Percent Change in Worst Pain Score
Time frame: at week 6
Weekly mean of 24 hour Worst Pain Score, percent change from baseline. Range is 0-10 with 0= no pain and 10= worst possible pain.
2 secondary outcomes
Percent Change in Average Pain Score.
Time frame: at week 6
Global Impression of Change
Time frame: Week 6 vs baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Multiple Sclerosis
RecruitingPhase 2
Metformin as an add-on or Monotherapy in Treatment of Aging People With Multiple Sclerosis (MS)
Multiple Sclerosis
RecruitingObservational study
Pain Phenotypes in Individuals With Multiple Sclerosis
Multiple Sclerosis, Chronic Pain
Not yet recruiting
Evaluating the Effect of the Zeen Mobility Device on Clinical Practicality, Safety, and Impact (Via Assessments of Walking, Standing Tolerance, Balance, Endurance, Effort, and Participation in Daily Tasks) in an Outpatient Rehabilitation Setting for Individuals With Mobility Impairments.
Stroke, Parkinson's Disease (PD)
RecruitingPhase 3
Dalfampridine Combined With Physical Therapy for Mobility Impairment in Multiple Sclerosis
Multiple Sclerosis
RecruitingPhase 2
Targeting Agonists of Glucagon-like Peptide-1 Receptor for Multiple Sclerosis
Multiple Sclerosis
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.
Theodore R Brown, MD.MPH principal investigator
Evergreen Healthcare
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Duloxetine in people with Multiple Sclerosis, run by Brown, Theodore R., M.D., MPH 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 18 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 27 Apr 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. 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 6 Apr 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?
Percent Change in Worst Pain Score (time frame: at week 6). 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 27 Apr 2015.