Fibromyalgia
Conditions
Brief summary
Use of the drug Milnacipran will reduce ventricular lactate levels and processing time for completing complex tasks relative to placebo.
Detailed description
Patients with Fibromyalgia will show elevated ventricular lactate levels as measured via magnetic resonance spectroscopy (MRS). Patients treated with Milnacipran will show normalization of ventricular lactate levels compared to those treated with placebo, and will also show normalization of the increased latency to respond to complex reaction time probes compared to those treated with placebo.
Interventions
DRUGMilnacipran
Patients will take an increasing number of 12.5mg pills for the first 9 days during the ramp up period and then take one 50mg pill in the morning and one 50mg pill in the evening for the remaining 8 weeks of the study.
DRUGPlacebo
Patients will take an increasing number of placebo pills for the first 9 days during the ramp up period and then take one pill in the morning and one in the evening for the remaining 8 weeks of the study.
Sponsors
Beth Israel Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 68 Years
Healthy volunteers
No
Inclusion criteria
* Female or male subjects who fulfill the American College of Rheumatology's case definition for Fibromyalgia. * 18 through 68 years of age
Exclusion criteria
* Pregnant or trying to become pregnant * Taking any other Serotonin Norepinephrine Reuptake Inhibitor (SNRI) or already taking milnacipran * Patients who do not indicate their pain levels as less than substantial despite their best care * History of any psychotic disorder or history of alcoholism or drug abuse within 10 years of intake as determined by psychiatric diagnostic interview * Presence of current depression as determined by psychiatric diagnostic interview * Presence of brain lesion on MRI anatomical study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Ventricular Lactate Levels in the Brain | Baseline and 2 months | Ventricular lactate levels will be assessed before and at the end of the trial using a scanning method known as magnetic resonance spectroscopy (MRS), which is used to determine the presence and quantity of a number of chemicals in the brain. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Cognitive Function Assessed by the no Cue Condition of the Attention Network Test (ANT). | Baseline and 2 months | The Attention Network Test (ANT) is a computerized test designed to evaluate the efficiency of the attention network. The ANT consists of a set of cued reaction time tasks to assess vigilance and efficiency to detect novel visual stimuli. The ANT also includes a set of flanker tasks during which a decision needs to be made about whether the orientation of a central stimulus is congruent or incongruent with a set of flanking arrows. Scores on the cued reaction time tasks (no cue, centre cue, double cue) reflect latency to respond measured in milliseconds (slower performance equals greater values). The score on the flanker task reflecting executive attention is derived by subtracting obtained latencies on the congruent flanker from the incongruent condition. Based on our prior work, we are hypothesizing that drug treated Ss will show improved performance on the no cue reaction time condition and on the derived executive attention variable compared to placebo treated. |
| Change in Widespread Pain | 2 months | Pain was assessed using a visual analog scale (VAS) ranging from 0 (no pain) to 10 (worst pain ever). The baseline value recorded was widespread pain at the time of assessment and the 2 months follow value recorded was widespread pain over the week prior to assessment. |
Countries
United States
Participant flow
Pre-assignment details
We got informed consent from 37 patients but excluded 3 -- 2 for saving psychiatric diagnoses that were exclusionary and one for having a metal implant which was an exclusion for neuroimaging. Thus 34 patients were randomized for the trial.
Participants by arm
| Arm | Count |
|---|---|
| Patients Taking the Drug Minalcipran Milnacipran: Patients will take an increasing number of 12.5mg pills for the first 9 days during the ramp up period and then take one 50mg pill in the morning and one 50mg pill in the evening for the remaining 8 weeks of the study. | 13 |
| Patients Taking the Placebo Placebo: Patients will take an increasing number of placebo pills for the first 9 days during the ramp up period and then take one pill in the morning and one in the evening for the remaining 8 weeks of the study. | 13 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 3 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Patients Taking the Drug Minalcipran | Total | Patients Taking the Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 26 Participants | 13 Participants |
| Age, Continuous | 48 years STANDARD_DEVIATION 4 | 47 years STANDARD_DEVIATION 4 | 47 years STANDARD_DEVIATION 5 |
| Region of Enrollment United States | 13 participants | 26 participants | 13 participants |
| Sex: Female, Male Female | 13 Participants | 26 Participants | 13 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 2 / 17 | 1 / 17 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 |
Outcome results
Primary
Change in Ventricular Lactate Levels in the Brain
Ventricular lactate levels will be assessed before and at the end of the trial using a scanning method known as magnetic resonance spectroscopy (MRS), which is used to determine the presence and quantity of a number of chemicals in the brain.
Time frame: Baseline and 2 months
Population: One drug treated and two placebo treated could not be analyzed due to excessive head motion
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Taking the Drug Minalcipran | Change in Ventricular Lactate Levels in the Brain | -0.87 international units (iu) | Standard Deviation 0.91 |
| Patients Taking the Placebo | Change in Ventricular Lactate Levels in the Brain | 0.32 international units (iu) | Standard Deviation 1.58 |
p-value: <0.05General Linear Model (GLM)
Secondary
Change in Cognitive Function Assessed by the no Cue Condition of the Attention Network Test (ANT).
The Attention Network Test (ANT) is a computerized test designed to evaluate the efficiency of the attention network. The ANT consists of a set of cued reaction time tasks to assess vigilance and efficiency to detect novel visual stimuli. The ANT also includes a set of flanker tasks during which a decision needs to be made about whether the orientation of a central stimulus is congruent or incongruent with a set of flanking arrows. Scores on the cued reaction time tasks (no cue, centre cue, double cue) reflect latency to respond measured in milliseconds (slower performance equals greater values). The score on the flanker task reflecting executive attention is derived by subtracting obtained latencies on the congruent flanker from the incongruent condition. Based on our prior work, we are hypothesizing that drug treated Ss will show improved performance on the no cue reaction time condition and on the derived executive attention variable compared to placebo treated.
Time frame: Baseline and 2 months
Population: Data from 4 were excluded due to 2 having error rates greater than 50%, indicating that they did not understand the task and 2 having simple reaction times longer than those for the complex reaction times on the ANT, suggesting their need for additional practice trials on the simple motor reaction time task.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Patients Taking the Drug Minalcipran | Change in Cognitive Function Assessed by the no Cue Condition of the Attention Network Test (ANT). | No cue condition | -79.56 latency to respond (msecs.) | Standard Deviation 80.45 |
| Patients Taking the Drug Minalcipran | Change in Cognitive Function Assessed by the no Cue Condition of the Attention Network Test (ANT). | Executive attention | -68.73 latency to respond (msecs.) | Standard Deviation 52.77 |
| Patients Taking the Placebo | Change in Cognitive Function Assessed by the no Cue Condition of the Attention Network Test (ANT). | Executive attention | -34.77 latency to respond (msecs.) | Standard Deviation 52.77 |
| Patients Taking the Placebo | Change in Cognitive Function Assessed by the no Cue Condition of the Attention Network Test (ANT). | No cue condition | -35.00 latency to respond (msecs.) | Standard Deviation 90.09 |
p-value: <0.05General Linear Model (GLM)
Secondary
Change in Widespread Pain
Pain was assessed using a visual analog scale (VAS) ranging from 0 (no pain) to 10 (worst pain ever). The baseline value recorded was widespread pain at the time of assessment and the 2 months follow value recorded was widespread pain over the week prior to assessment.
Time frame: 2 months
Population: Data from all 26 participants were used for analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Patients Taking the Drug Minalcipran | Change in Widespread Pain | -1.24 units on a scale | Standard Deviation 1.57 |
| Patients Taking the Placebo | Change in Widespread Pain | 0.66 units on a scale | Standard Deviation 1.75 |
p-value: <0.05Wilcoxon (Mann-Whitney)