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

NCT ID: NCT01829243

Last Updated: 2023-10-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2013-05-31

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.

Conditions

Fibromyalgia; Neurocognition

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Milnacipran

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.

Group Type: EXPERIMENTAL

Milnacipran

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Placebo

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.

Group Type: PLACEBO_COMPARATOR

Milnacipran

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Interventions

Milnacipran

Intervention Type: DRUG

Placebo

Intervention Type: DRUG

Other Intervention Names

Savella

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Forest Laboratories

INDUSTRY

Sponsor Role: collaborator

Duke University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ashwin A Patkar, MD

Role: PRINCIPAL_INVESTIGATOR

Duke University

Locations

Duke University Medical Center / Civitan Building

Durham, North Carolina, United States

Countries

United States

References

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.

Reference Type: DERIVED

PMID: 24800123 (View on PubMed)

Other Identifiers

Pro00026392

Identifier Type: -

Identifier Source: org_study_id