Sleep DisordersPhase 4NCT01234675

The Effects of Milnacipran on Sleep Disturbance in Fibromyalgia

A Phase 4 study testing Milnacipran in people with Sleep Disorders and Fibromyalgia, run by Mansoor Ahmed M.D. 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 years and older
Conditions the study is for: Sleep Disorders, Fibromyalgia, Sleep
What is being tested?: Milnacipran
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 19 participants
Where: 1 siteUnited States
Study dates: Nov 2010to Feb 2014
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

Men or women at least 18 years or older
Diagnosis of fibromyalgia
Clinically significant sleep disturbance, defined as difficulty in maintaining sleep (wake after sleep onset and arousal index) at least three times per week for at least one month
Understand and willing to cooperate with the study procedures
Maintain a normal sleep schedule, with daytime-awake and nighttime-sleep schedule, with customary bedtime between 9 PM and midnight, and rise time 5 AM and 9 AM
Patients who are able to speak, read, and understand English language and able to follow the study protocol, and are able to sign the informed consent

Who cannot join

Subject has any of the following medical conditions:
Liver disease, blood disorder, autoimmune disease, endocrine, cardiovascular, hypertension, renal, hepatic, gastrointestinal, or neurological disorder, active peptic ulcer or inflammatory bowel disease
Significant sleep apnea
Periodic leg movement disorder (PLMD) or restless legs syndrome (RLS)
Any form of severe psychiatric illness, moderate to severe depression, including significant risk of suicide
Patients with uncontrolled glaucoma

Show all 15Show fewer

Inability to discontinue the prohibited medications
Female of childbearing potential not using birth control measures; or lactating.
History of alcohol, narcotic, benzodiazepines or other substance abuse within the past one year.
Patient on prohibited medication will include but not limited to:
Anxiolytics, anti-convulsants, antipsychotics, lithium, barbiturates, anti-histamines, monoamine oxidase inhibitors, or medications that affect sleep
Any prescription or over the counter stimulants
Medications that are contraindicated with the use of milnacipran
Excessive caffeine use, defined as a consumption of more than 500 mg of caffeine or other xanthines, smoking >1/2 a pack/day or alcohol use >14 units/week
History of allergy to milnacipran.

Trial locations and contacts

1 site in 1 country.

United States1 site

Cleveland Sleep Research Center
Middleburg Heights, Ohio, 44130

Other trials in United States

About this study

Fibromyalgia is a condition of chronic widespread pain, sleep disturbance and fatigue. Most of the patients with fibromyalgia complain of either non-restorative sleep or complaints of disturbed sleep due to pain. The study aimed at examining the effects of milnacipran on sleep disturbance in patients with fibromyalgia. The study is a randomized, double-blind, placebo controlled, two way crossover polysomnography (PSG) study to explore the effects of milnacipran on sleep disturbance. Patients received either milnacipran 50 mg twice a day (BID) or matching placebo.

Read the detailed description

The sleep disturbance in fibromyalgia is characterized as non-restorative in nature, and is defined as a feeling of light sleep, independent of duration, and as non-refreshing. As such, these patients wake up in the morning and complain of stiffness and overall aching of the body.

It is well known that reciprocal relationship exists between sleep and pain, with sleep disturbances being an important contributor to morbidity in fibromyalgia. Milnacipran, a selective serotonin norepinephrine receptor inhibitor (SNRI), was approved by the Food and Drug Administration (FDA) for the management of fibromyalgia. Although milnacipran has extensively been studied in fibromyalgia patients, but there is no objective measure, i.e., the use of overnight polysomnography, to determine its effects on sleep.

The study was undertaken to evaluate the effects of milnacipran on PSG determined measures of sleep in patients with fibromyalgia. The study also evaluated the impact of milnacipran on subjective measures of sleep and fibromyalgia symptoms.

Conditions: Sleep Disorders, Fibromyalgia, Sleep
Being tested: Milnacipran, Placebo
Keywords: Fibromyalgia, Sleep disorders, Forest Laboratories, Milnacipran
Medical subject headings: Sleep Wake Disorders, Fibromyalgia

What participants receive

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

MilnacipranDrug
Also called Savella
50 mg twice daily
PlaceboDrug
Also called Sugar pill
50 mg twice daily

Study groups in NCT01234675
Study group	Role	What they receive
milnacipran	Experimental	Drug: milnacipran 7-day dose escalation, 28- day treatment with milnacipran 50 mg and 7-day taper period before or after crossover to placebo Receives: Drug: Milnacipran
placebo	Placebo comparator	Drug: placebo 45-day placebo treatment before or after crossover to milnacipran Receives: Drug: Placebo

What is being measured

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

Number of Awakenings After Sleep Onset (NAASO)
Number of awakenings after defined sleep onset until lights on.
Measured: 4-Week maintenance treatment with milnacipran and placebo
Sleep Efficiency (SE)
Percentage of time spent asleep while in bed
Measured: 4-Week maintenance treatment with milnacipran and placebo
Wake After Sleep Onset (WASO)
Wake time after defined sleep onset until lights on.
Measured: 4-Week maintenance treatment with milnacipran and placebo

Secondary outcomes (10)

Latency to Persistent Sleep Onset (LPS)
It is defined as time from lights out to the first consecutive 2 minutes of uninterrupted sleep.
Measured: 4-Week treatment with milnacipran and placebo
Total Sleep Time (TST)
Total sleep of all Rapid Eye Movement (REM) and Non- Rapid Eye Movement Sleep (NTREM) from lights out to lights on.
Measured: 4-Week treatment with milnacipran and placebo
Arousal Index (AI)
Number of arousals per hour of sleep
Measured: 4-Week treatment with milnacipran and placebo
Slow Wave Sleep (SWS)
Time spent in stage 3 of non-rapid eye movement sleep and often referred to as deep sleep.
Measured: 4-Week treatment with milnacipran and placebo
Sleep Problem Index 2, Medical Outcomes Study Sleep Scale (MOS-SS)
This is a subjective index derived from the medical outcomes study sleep scale (MOS-SS) scored on a 0-100 possible range with higher scores indicating more severe sleep disruption. The scale is a self-report instrument consisting of 12 items that assess perceived initiation and maintenance of sleep, respiratory problems during sleep, sleep duration, perceived adequacy of sleep and daytime somnolence.
Measured: 4-Week treatment with milnacipran and placebo
Sleep Quality Scale
Sleep quality measure derived from daily sleep diary rating ranging from 0 ("very poor") to 10 ("excellent")
Measured: 4-Week treatment with milnacipran and placebo
Fatigue Severity Scale (FSS) Total Score
The scale is a 9-item self-report of fatigue in the past week and scored on a 7-point scale with 1 = strongly disagree and 7 = strongly agree. Scores range from 9 to 63 with higher scores indicating higher fatigue severity. A total score greater or equal to 36 suggests fatigue.
Measured: 4-Week treatment with milnacipran and placebo
Fibromyalgia Impact Questionnaire (FIQ) Total Score
The scale is composed of 10 items relating to fibromyalgia symptoms experienced in the past week. Score ranges from 0 to 100 with higher scores indicating a greater effect of fibromyalgia on a person's life.
Measured: 4-Week treatment with milnacipran and placebo
Brief Pain Inventory (BPI) Mean Severity Score
The score is derived from the BPI scale and measures pain intensity in the past 24 hour. The pain severity score is derived as the average score of 4 pain items assessing pain at its "worst", "least", "average" and "now" and ranges from 0-10 with higher scores reflecting greater pain
Measured: 4-Week treatment with milnacipran and placebo
Brief Pain Inventory (BPI) Mean Interference Score
The score is derived from the BPI scale and measures the effect of pain on functioning in the past 24 hour. It is the average score of 7 items interfering with general activity, mood, walking ability, normal work, relations with other people, sleep and enjoyment of life. Score ranges from 0-10 with higher scores reflecting greater interference.
Measured: 4-Week treatment with milnacipran and placebo

Timeline

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

Nov 2010Feb 2014

First posted4 Nov 2010 (estimated)
Study startNov 2010
Primary completionFeb 2014
Study completionFeb 2014

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 Sleep DisordersStudies 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: Crossover
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 19 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT01234675
Sponsor's protocol ID: SAV-MD-17
Status last verified: Aug 2019
First submitted: 3 Nov 2010
Last updated: 21 Aug 2019
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Ahmed M, Aamir R, Jishi Z, Scharf MB. The Effects of Milnacipran on Sleep Disturbance in Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled, Two-Way Crossover Study. J Clin Sleep Med. 2016 Jan;12(1):79-86. doi: 10.5664/jcsm.5400.
PubMed 26414990

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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Study at a glance

From the registry record, last updated by the sponsor on 21 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: The Effects of Milnacipran on Sleep Disturbance in Fibromyalgia
ClinicalTrials.gov ID: NCT01234675
Acronym / sponsor ID: SAV-MD-17
Conditions: Sleep Disorders, Fibromyalgia, Sleep
Keywords: Fibromyalgia, Sleep disorders, Forest Laboratories, Milnacipran
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 19 participants (actual)
Lead sponsor: Mansoor Ahmed M.D.University, hospital or other
Collaborators: Forest Laboratories
Study start: Nov 2010
Primary completion: Feb 2014 (actual)
Study completion: Feb 2014 (actual)
First posted: 4 Nov 2010 (estimated)
Results: Posted 22 Jul 2015

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, investigator)
Number of arms: 2

Arm	Type	Receives
milnacipran	Experimental	Drug: MilnacipranDrug: milnacipran 7-day dose escalation, 28- day treatment with milnacipran 50 mg and 7-day taper period before or after crossover to placebo
placebo	Placebo comparator	Drug: PlaceboDrug: placebo 45-day placebo treatment before or after crossover to milnacipran

Who may qualify

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

Key inclusion criteria (6 listed)

Men or women at least 18 years or older
Diagnosis of fibromyalgia
Clinically significant sleep disturbance, defined as difficulty in maintaining sleep (wake after sleep onset and arousal index) at least three times per week for at least one month
Understand and willing to cooperate with the study procedures
Maintain a normal sleep schedule, with daytime-awake and nighttime-sleep schedule, with customary bedtime between 9 PM and midnight, and rise time 5 AM and 9 AM

Key exclusion criteria (15 listed)

Subject has any of the following medical conditions:
Liver disease, blood disorder, autoimmune disease, endocrine, cardiovascular, hypertension, renal, hepatic, gastrointestinal, or neurological disorder, active peptic ulcer or inflammatory bowel disease
Significant sleep apnea
Periodic leg movement disorder (PLMD) or restless legs syndrome (RLS)
Any form of severe psychiatric illness, moderate to severe depression, including significant risk of suicide

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: Savella50 mg twice daily	Drug	milnacipran
PlaceboAlso: Sugar pill50 mg twice daily	Drug	placebo

Primary outcome

Number of Awakenings After Sleep Onset (NAASO)
Time frame: 4-Week maintenance treatment with milnacipran and placebo
Number of awakenings after defined sleep onset until lights on.
Sleep Efficiency (SE)
Time frame: 4-Week maintenance treatment with milnacipran and placebo
Percentage of time spent asleep while in bed
Wake After Sleep Onset (WASO)
Time frame: 4-Week maintenance treatment with milnacipran and placebo
Wake time after defined sleep onset until lights on.

10 secondary outcomes

Latency to Persistent Sleep Onset (LPS)
Time frame: 4-Week treatment with milnacipran and placebo
Total Sleep Time (TST)
Time frame: 4-Week treatment with milnacipran and placebo
Arousal Index (AI)
Time frame: 4-Week treatment with milnacipran and placebo
Slow Wave Sleep (SWS)
Time frame: 4-Week treatment with milnacipran and placebo
Sleep Problem Index 2, Medical Outcomes Study Sleep Scale (MOS-SS)
Time frame: 4-Week treatment with milnacipran and placebo
Sleep Quality Scale
Time frame: 4-Week treatment with milnacipran and placebo
Fatigue Severity Scale (FSS) Total Score
Time frame: 4-Week treatment with milnacipran and placebo
Fibromyalgia Impact Questionnaire (FIQ) Total Score
Time frame: 4-Week treatment with milnacipran and placebo
Brief Pain Inventory (BPI) Mean Severity Score
Time frame: 4-Week treatment with milnacipran and placebo
Brief Pain Inventory (BPI) Mean Interference Score
Time frame: 4-Week treatment with milnacipran and placebo

Results and safety

Results posted to the registry on 22 Jul 2015, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Placebo Then Milnacipran	10	9
Milnacipran Then Placebo	9	8

Primary outcome: Number of Awakenings After Sleep Onset (NAASO)

Time frame: 4-Week maintenance treatment with milnacipran and placebo. Mean (Standard Error). Unit: Awakenings

Measure	Milnacipran n = 15	Placebo n = 15
Value	39.5 (4.5)	34.9 (4.2)

Milnacipran vs Placebo: Paired difference: 4.6 (95% CI -7.3 to 16.6), p = 0.424, Paired T test

Population analysed: 15 subjects completed the study

Primary outcome: Sleep Efficiency (SE)

Time frame: 4-Week maintenance treatment with milnacipran and placebo. Mean (Standard Error). Unit: percentage of total sleep time

Measure	Milnacipran n = 15	Placebo n = 15
Value	77.1 (3.8)	83.3 (2.3)

Milnacipran: Paired difference: -6.1 (95% CI -12.2 to -0.04), p = 0.049, Paired T test

Primary outcome: Wake After Sleep Onset (WASO)

Time frame: 4-Week maintenance treatment with milnacipran and placebo. Mean (Standard Error). Unit: minutes

Measure	Milnacipran n = 15	Placebo n = 15
Value	76.2 (10.8)	53.6 (8.1)

Milnacipran vs Placebo: Paired difference: 22.6 (95% CI -0.6 to 45.8), p = 0.056, Paired T test

10 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse event data was collected on and after Day 1 of the first treatment period. The data collection continued till the two weeks after the second treatment period.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Milnacipran	0 of 19 (0%)	12 of 19 (63.2%)	Not reported
Placebo	1 of 19 (5.3%)	10 of 19 (52.6%)	Not reported

Limitations and caveats (from the sponsor): A well-established adaptation and re-adaptation to laboratory effects may have compromised our results. Other study biases include biases inherent in the crossover design, and a small sample size.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2019.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 26414990Ahmed M, Aamir R, Jishi Z, Scharf MB. The Effects of Milnacipran on Sleep Disturbance in Fibromyalgia: A Randomized, Double-Blind, Placebo-Controlled, Two-Way Crossover Study. J Clin Sleep Med. 2016 Jan;12(1):79-86. doi: 10.5664/jcsm.5400.

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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.

Mansoor Ahmed, MD principal investigator

Cleveland Sleep Research Cneter

Rozina Aamir, MS, MBA study director

Cleveland Sleep Research Center

Noel Cyrill, MD study director

SouthWest Cleveland Sleep Center

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 Milnacipran in people with Sleep Disorders and Fibromyalgia, run by Mansoor Ahmed M.D. 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 15 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 21 Aug 2019. 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 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 Jul 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?

Number of Awakenings After Sleep Onset (NAASO) (time frame: 4-Week maintenance treatment with milnacipran and placebo). 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 NCT01234675, 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 21 Aug 2019.