Clinical trial NCT01829243: Milnacipran and Neurocognition, Pain and Fatigue in Fibromyalgia : A 13-week Randomized, Placebo Controlled Cross Over Trial
Official title: Milnacipran and Neurocognition, Pain and Fatigue in Fibromyalgia: A 13-week Randomized, Placebo Controlled Cross Over Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Fibromyalgia
Neurocognition
Keywords: Milnacipran
Fibromyalgia
Neurocognition
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: Forest Laboratories
First posted: 2013-04-11
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.
* 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.

Primary outcomes:
measure: Visual Analogue Scale for Pain
timeFrame: Baseline, Week 1, 2,4, and 6 weeks
measure: Changes in The Fatigue Severity Scale (FSS)
timeFrame: Baseline, Week 1, 2,4, and 6 weeks
measure: Composite Brief Assessment of Cognition (BAC) Score
timeFrame: Baseline, Week 6
Secondary outcomes:
measure: MATRICS Consensus Cognitive Battery Composite Score
timeFrame: Baseline, Week 6
Other outcomes:
Locations:
city: Durham
country: United States
facility: Duke University Medical Center / Civitan Building
state: North Carolina
Study officials:
affiliation: Duke University
name: Ashwin A Patkar, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.