Back to resultsMilnacipran and Neurocognition, Pain and Fatigue in Fibromyalgia : A 13-week Randomized, Placebo Controlled Cross Over Trial
Primary Purpose
Fibromyalgia, Neurocognition
Status
Completed
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
Milnacipran
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Fibromyalgia focused on measuring Milnacipran, Fibromyalgia, 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.
Sites / Locations
- Duke University Medical Center / Civitan Building
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Milnacipran
Placebo
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
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.
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.
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.
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT01829243
First Posted
April 9, 2013
Last Updated
August 27, 2014
Sponsor
Duke University
Collaborators
Forest Laboratories
1. Study Identification
Unique Protocol Identification Number
NCT01829243
Brief Title
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
2. Study Status
Record Verification Date
August 2014
Overall Recruitment Status
Completed
Study Start Date
July 2011 (undefined)
Primary Completion Date
May 2013 (Actual)
Study Completion Date
May 2013 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
Collaborators
Forest Laboratories
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Fibromyalgia, Neurocognition
Keywords
Milnacipran, Fibromyalgia, Neurocognition
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Masking
ParticipantOutcomes Assessor
Allocation
Randomized
Enrollment
26 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Milnacipran
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Milnacipran
Other Intervention Name(s)
Savella
Intervention Type
Drug
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
Visual Analogue Scale for Pain
Description
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.
Time Frame
Baseline, Week 1, 2,4, and 6 weeks
Title
Changes in The Fatigue Severity Scale (FSS)
Description
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.
Time Frame
Baseline, Week 1, 2,4, and 6 weeks
Title
Composite Brief Assessment of Cognition (BAC) Score
Description
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.
Time Frame
Baseline, Week 6
Secondary Outcome Measure Information:
Title
MATRICS Consensus Cognitive Battery Composite Score
Description
(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.
Time Frame
Baseline, Week 6
10. Eligibility
Sex
All
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Ashwin A Patkar, MD
Organizational Affiliation
Duke University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Medical Center / Civitan Building
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
24800123
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.
Results Reference
derived
Learn more about this trial
Milnacipran and Neurocognition, Pain and Fatigue in Fibromyalgia : A 13-week Randomized, Placebo Controlled Cross Over Trial
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