FibromyalgiaPhase 3NCT01829243

Milnacipran and Neurocognition, Pain and Fatigue in Fibromyalgia : A 13-week Randomized, Placebo Controlled Cross Over Trial

A Phase 3 study testing Milnacipran in people with Fibromyalgia and Neurocognition, run by Duke University at 1 site in United States.

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

Who is it for?: Ages 18 to 65 years
Conditions the study is for: Fibromyalgia, Neurocognition
What is being tested?: Milnacipran
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 26 participants
Where: 1 siteUnited States
Study dates: Jul 2011to May 2013
Phase: Phase 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 to 65 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Age 18 to 65 years.
Specific diagnosis of FM by the participant's rheumatologist or physician, including written confirmation, from a physician, of the FM diagnosis.
Confirmation of the FM diagnosis by American College of Rheumatology Criteria and a physical tender point examination.
Ability to give informed consent.
If female, nonpregnant/nonlactating.
If a sexually active female of reproductive potential, must be using adequate contraception (i.e., oral contraceptives, barrier protection, or prior tubal ligation) during the trial.

Who cannot join

Bipolar disorders, any psychotic disorder.
the existence of concomitant rheumatological disorders, including rheumatoid arthritis, systemic lupus erythematosus, Hashimoto's disease, Sjogren's syndrome or scleroderma.
Substance dependence (except nicotine dependence) in the previous 3 months.
Currently suicidal or high suicide risk.
Serious or unstable medical disorders.
Any psychotropic drug treatment in the previous 2 weeks before screening.

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A positive urine pregnancy test.
Screening laboratory values three times the limits of normal or judged clinically significant by the investigator.
History of hypersensitivity to milnacipran.
Seizure disorder, traumatic brain injury, any CNS disorder that affects cognitive status.
Concomitant meds: A minimum of 30 days on stable dose of analgesics and a minimum of 4 week washout from antidepressants and fibromyalgia specific medication ( e.g. pregabalin, neurontin) and supplements ( St John's wort, SAM-E).
Narrow angle glaucoma.

Trial locations and contacts

1 site in 1 country.

United States1 site

Duke University Medical Center / Civitan Building
Durham, North Carolina, 27705

Other trials in United States

About this study

Official title: Milnacipran and Neurocognition, Pain and Fatigue in Fibromyalgia: A 13-week Randomized, Placebo Controlled Cross Over Trial

This study was designed to investigate whether milnacipran is safe and effective in improving cognitive function in fibromyalgia. In addition, this study was aimed to investigate whether improvement in neurocognitive status due to milnacipran correlates with improvements in pain, to investigate whether improvement in neurocognitive status due to milnacipran correlates with improvements in fatigue, and to determine whether treatment with improvement in neurocognitive status, pain and fatigue correlates with functional improvement.

Read the detailed description

Cognitive dysfunction is observed in fibromyalgia, especially for episodic memory, learning, and working memory.There is evidence for dysregulation of the attention system from low-level sensory processes up to emotional processes, and increased sensitivity to distraction.Milnacipran's balance of norepinephrine (NE) to serotonin (5-HT) of 3:1, similar to amitriptyline, a tricyclic that has demonstrated efficacy in fibromyalgia, as compared to venlafaxine which is 1:30, or duloxetine which is 1:10.7 In addition, because of milnacipran's effect on 5-HT, it should also be effective in treating other symptoms such as sleep disturbances and mood changes, which are associated to fibromyalgia, as well as other functional somatic syndromes. It is worth noting that several medications to treat fibromyalgia are sedating (e.g pregabalin, opioids, muscle relaxants) and impair neurocognition.

Conditions: Fibromyalgia, Neurocognition
Being tested: Milnacipran, Placebo
Keywords: Milnacipran, Fibromyalgia, Neurocognition
Medical subject headings: Fibromyalgia

What participants receive

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

MilnacipranDrug
Also called Savella
PlaceboDrug

Study groups in NCT01829243
Study group	Role	What they receive
Milnacipran	Experimental	Eligible subjects will receive milnacipran (12.5 mg-200 mg/day) in the forces titration schedule in flexible doses to the maximum tolerated dose starting with 12.5 mg qd for 1 day, 12.5 mg bid for 2 days, 25 mg bid for 4 days, 50 mg bid for 7 days and 100 mg bid thereafter. Patients who cannot tolerate higher doses will have a step-wise reduction in doses (e.g. 200 mg/day dose will be reduced to 100 mg/day; 100 mg/day will be reduced to 50 mg/day). Drug will be discontinued at the end of the study. Receives: Drug: Milnacipran; Drug: Placebo
Placebo	Placebo comparator	Eligible subjects will receive placebo (12.5 mg-200 mg/day) in the forces titration schedule in flexible doses to the maximum tolerated dose starting with 12.5 mg qd for 1 day, 12.5 mg bid for 2 days, 25 mg bid for 4 days, 50 mg bid for 7 days and 100 mg bid thereafter. Patients who cannot tolerate higher doses will have a step-wise reduction in doses (e.g. 200 mg/day dose will be reduced to 100 mg/day; 100 mg/day will be reduced to 50 mg/day). Drug will be discontinued at the end of the study. Receives: Drug: Milnacipran; Drug: Placebo

What is being measured

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

Visual Analogue Scale for Pain
Visual Analogue Scale for Pain operationally is a 100 mm line anchored by word descriptors at each end. The patient marks a point on the line that reflects their current pain state. The distance in mm from the left anchor point is the score. Higher scores indicate more pain.
Measured: Baseline, Week 1, 2,4, and 6 weeks
Changes in The Fatigue Severity Scale (FSS)
The Fatigue Severity Scale (FSS) is composed of nine items with a seven-point response format. The minimum score = 9 and maximum score possible = 63. Higher scores = greater fatigue severity.
Sample questions include "I am easily fatigued" and "Exercise brings on my fatigue." In the initial validation study, internal consistency for the Fatigue Severity Scale was high for specific illness groups (MS and lupus) and healthy controls. The scale clearly distinguished patients from controls and it was moderately correlated with a single-item visual analogue scale of fatigue intensity. In all patients, clinical improvement in fatigue was associated with reductions in scores on the Fatigue Severity Scale. The Fatigue Severity Scale is also a practical measure due to its brevity and ease of administration and scoring.
Measured: Baseline, Week 1, 2,4, and 6 weeks
Composite Brief Assessment of Cognition (BAC) Score
The composite BAC score is calculated by scoring each of the 6 individual tests (Verbal Memory Recall, Digit Sequencing, Token Motor Task, Verbal Fluency, Symbol Coding, and Tower of London), comparing each score to a healthy control sample to create z-scores, summing the z-scores, and rescaling the sum. The composite score range is -2127.8 to 1878.8, with higher scores indicating better cognition.
Measured: Baseline, Week 6

Secondary outcomes (1)

MATRICS Consensus Cognitive Battery Composite Score
(MATRICS) Consensus Cognitive Battery measures cognitive functioning within 7 domains: speed of processing, attention/vigilance, working memory (non verbal and verbal), verbal learning, visual learning, reasoning and problem solving and social cognition.
The composite score is calculated by the MATRICS computer program, which equally weights each of the 7 domain scores. The range of composite scores is 20-80. Higher scores indicate higher levels or cognitive functioning, while lower scores indicate lower levels of cognitive functioning.
Measured: Baseline, Week 6

Timeline

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

Jul 2011May 2013

First posted11 Apr 2013 (estimated)
Study startJul 2011
Primary completionMay 2013
Study completionMay 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 FibromyalgiaStudies 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 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind
Who is masked: Participant, Outcomes assessor
Enrolment: 26 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01829243
Sponsor's protocol ID: Pro00026392
Status last verified: Aug 2014
First submitted: 9 Apr 2013
Last updated: 26 Oct 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Kim JL, Rele S, Marks DM, Masand PS, Yerramsetty P, Millet RA, Keefe RS, Patkar AA. Effects of milnacipran on neurocognition, pain, and fatigue in fibromyalgia: a 13-week, randomized, placebo-controlled, crossover trial. Prim Care Companion CNS Disord. 2013;15(6):PCC.13m01555. doi: 10.4088/PCC.13m01555. Epub 2014 Dec 26.
PubMed 24800123

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 Fibromyalgia trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Milnacipran and Neurocognition, Pain and Fatigue in Fibromyalgia: A 13-week Randomized, Placebo Controlled Cross Over Trial
ClinicalTrials.gov ID: NCT01829243
Acronym / sponsor ID: Pro00026392
Conditions: Fibromyalgia, Neurocognition
Keywords: Milnacipran, Fibromyalgia, Neurocognition
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 26 participants (actual)
Lead sponsor: Duke UniversityUniversity, hospital or other
Collaborators: Forest Laboratories
Study start: Jul 2011
Primary completion: May 2013 (actual)
Study completion: May 2013 (actual)
First posted: 11 Apr 2013 (estimated)
Results: Posted 29 Aug 2014

Clinical summary

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

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Double blind (participant, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Milnacipran	Experimental	Drug: Milnacipran, Drug: PlaceboEligible subjects will receive milnacipran (12.5 mg-200 mg/day) in the forces titration schedule in flexible doses to the maximum tolerated dose starting with 12.5 mg qd for 1 day, 12.5 mg bid for 2 days, 25 mg bid for 4 days, 50 mg bid for 7 days and 100 mg bid thereafter. Patients who cannot tolerate higher doses will have a step-wise reduction in doses (e.g. 200 mg/day dose will be reduced to 100 mg/day; 100 mg/day will be reduced to 50 mg/day). Drug will be discontinued at the end of the study.
Placebo	Placebo comparator	Drug: Milnacipran, Drug: PlaceboEligible subjects will receive placebo (12.5 mg-200 mg/day) in the forces titration schedule in flexible doses to the maximum tolerated dose starting with 12.5 mg qd for 1 day, 12.5 mg bid for 2 days, 25 mg bid for 4 days, 50 mg bid for 7 days and 100 mg bid thereafter. Patients who cannot tolerate higher doses will have a step-wise reduction in doses (e.g. 200 mg/day dose will be reduced to 100 mg/day; 100 mg/day will be reduced to 50 mg/day). Drug will be discontinued at the end of the study.

Who may qualify

Ages: 18 to 65 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (6 listed)

Age 18 to 65 years.
Specific diagnosis of FM by the participant's rheumatologist or physician, including written confirmation, from a physician, of the FM diagnosis.
Confirmation of the FM diagnosis by American College of Rheumatology Criteria and a physical tender point examination.
Ability to give informed consent.
If female, nonpregnant/nonlactating.

Key exclusion criteria (12 listed)

Bipolar disorders, any psychotic disorder.
the existence of concomitant rheumatological disorders, including rheumatoid arthritis, systemic lupus erythematosus, Hashimoto's disease, Sjogren's syndrome or scleroderma.
Substance dependence (except nicotine dependence) in the previous 3 months.
Currently suicidal or high suicide risk.
Serious or unstable medical disorders.

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	Drug	Milnacipran, Placebo
Placebo	Drug	Milnacipran, Placebo

Primary outcome

Visual Analogue Scale for Pain
Time frame: Baseline, Week 1, 2,4, and 6 weeks
Visual Analogue Scale for Pain operationally is a 100 mm line anchored by word descriptors at each end. The patient marks a point on the line that reflects their current pain state. The distance in mm from the left anchor point is the score. Higher scores indicate more pain.
Changes in The Fatigue Severity Scale (FSS)
Time frame: Baseline, Week 1, 2,4, and 6 weeks
The Fatigue Severity Scale (FSS) is composed of nine items with a seven-point response format. The minimum score = 9 and maximum score possible = 63. Higher scores = greater fatigue severity. Sample questions include "I am easily fatigued" and "Exercise brings on my fatigue." In the initial validation study, internal consistency for the Fatigue Severity Scale was high for specific illness groups (MS and lupus) and healthy controls. The scale clearly distinguished patients from controls and it was moderately correlated with a single-item visual analogue scale of fatigue intensity. In all patients, clinical improvement in fatigue was associated with reductions in scores on the Fatigue Severity Scale. The Fatigue Severity Scale is also a practical measure due to its brevity and ease of administration and scoring.
Composite Brief Assessment of Cognition (BAC) Score
Time frame: Baseline, Week 6
The composite BAC score is calculated by scoring each of the 6 individual tests (Verbal Memory Recall, Digit Sequencing, Token Motor Task, Verbal Fluency, Symbol Coding, and Tower of London), comparing each score to a healthy control sample to create z-scores, summing the z-scores, and rescaling the sum. The composite score range is -2127.8 to 1878.8, with higher scores indicating better cognition.

1 secondary outcome

MATRICS Consensus Cognitive Battery Composite Score
Time frame: Baseline, Week 6

Results and safety

Results posted to the registry on 29 Aug 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Milnacipran First, Then Placebo	11	7
Placebo First, Then Milnacipran	15	13

Primary outcome: Visual Analogue Scale for Pain

Time frame: Baseline, Week 1, 2,4, and 6 weeks. Mean (Full Range). Unit: mm

Measure	Milnacipran n = 20	Placebo n = 20
Week 0	59.4 (4.5 to 59.5)	68.6 (3.9 to 69.4)
Week 1	58.5 (3.4 to 59.1)	66.2 (3.4 to 67.3)
Week 2	55.7 (3.0 to 56.3)	61.5 (3.1 to 62.6)
Week 4	56.9 (2.7 to 57.1)	54.4 (2.8 to 55.2)
week 6	54.4 (2.7 to 55.9)	60.4 (2.5 to 60.5)

Population analysed: Analysis employed Intent-to-Treat with Last Observation Carried Forward (LOCF) analysis. The Intent-to-Treat group (ITT) was comprised of all subjects who received at least one dose of the medication.

Primary outcome: Changes in The Fatigue Severity Scale (FSS)

Time frame: Baseline, Week 1, 2,4, and 6 weeks. Mean (Full Range). Unit: units on a scale

Measure	Milnacipran n = 20	Placebo n = 20
Week 0	56.3 (44.0 to 56.7)	49.2 (44.0 to 49.2)
Week 1	54.0 (44.0 to 54.5)	53.4 (44.0 to 53.6)
Week 2	53.7 (44.0 to 53.7)	52.2 (44.0 to 52.5)
Week 4	54.1 (44.0 to 54.5)	52.8 (44.0 to 53.1)
Week 6	52.1 (44.0 to 52.5)	53.0 (44.0 to 53.7)

Primary outcome: Composite Brief Assessment of Cognition (BAC) Score

Time frame: Baseline, Week 6. Mean (Standard Deviation). Unit: units on a scale

Measure	Milnacipran n = 20	Placebo n = 20
Baseline	41.2 (7.3)	40.9 (10.4)
Week 6	42.9 (8.0)	42.9 (7.8)

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Milnacipran	0 of 20 (0%)	12 of 20 (60%)	Not reported
Placebo	0 of 20 (0%)	18 of 20 (90%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 24800123Kim JL, Rele S, Marks DM, Masand PS, Yerramsetty P, Millet RA, Keefe RS, Patkar AA. Effects of milnacipran on neurocognition, pain, and fatigue in fibromyalgia: a 13-week, randomized, placebo-controlled, crossover trial. Prim Care Companion CNS Disord. 2013;15(6):PCC.13m01555. doi: 10.4088/PCC.13m01555. Epub 2014 Dec 26.

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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.

Ashwin A Patkar, 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 3 study testing Milnacipran in people with Fibromyalgia and Neurocognition, 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 6 inclusion and 12 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 26 Oct 2023. 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 phase mean?

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 29 Aug 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?

Visual Analogue Scale for Pain (time frame: Baseline, Week 1, 2,4, and 6 weeks). The study lists 3 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 NCT01829243, 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 26 Oct 2023.