Effect of Milnacipran on Pain in Fibromyalgia (Forest)
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|ClinicalTrials.gov Identifier: NCT01288807|
Recruitment Status : Completed
First Posted : February 2, 2011
Results First Posted : September 24, 2019
Last Update Posted : September 24, 2019
|Condition or disease||Intervention/treatment||Phase|
|Fibromyalgia||Drug: Milnacipram||Phase 4|
Fibromyalgia (FM) is a chronic pain condition with significant morbidity. Current research suggests a primarily central mediation of the widespread pain including central sensitization at the spinal level and abnormal pain processing at the cerebral level. Findings in FM patients include abnormal neurotransmitter levels in cerebrospinal fluid (CSF), abnormal activation of cerebral pain processing areas and abnormal peripheral pain and sensory thresholds. Continuous low level spinal cord activation by primary nociceptive afferents (C and A delta fibers) is believed to significantly drive the central sensitization. One major spinal neurotransmitter released by these pain fibers is substance P (SP). Several studies have shown that FM patients have up to three times higher baseline SP levels in the CSF compared to controls. Since spinal neurotransmitter release and therefore nociceptive afferent activity is also regulated via a descending inhibitory pathway releasing norepinephrine (NE) and serotonin (5HT), decreased activity of this pain modulating system could also be involved in abnormal pain processing in FM. Indeed, there is support in the literature for decreased CSF levels of both NE and 5HT or their metabolites. Milnacipran, a NE and 5HT reuptake inhibitor, has been shown to potentially effectively reduce FM pain and symptoms of FM by affecting the above pathologies.
The investigators propose an open label clinical trial with milnacipran 200 mg over 12-weeks in order to investigate the pain pathway in FM patients at peripheral and spinal levels before and after treatment. In addition, the investigators will assess pain intensity and symptoms of FM before, during and after treatment. To determine if there are peripheral effects, the investigators will characterize the systemic neurotransmitter release and their metabolites in plasma. The investigators will also measure the heart rate variability using an electrocardiogram to look for effects on the sympathetic nervous system.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||8 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Effects of a 12 Week Milnacipran 200 mg Treatment on Pain Perception and Pain Processing in Fibromyalgia - An Open Label Study|
|Study Start Date :||February 2011|
|Actual Primary Completion Date :||January 2015|
|Actual Study Completion Date :||January 2015|
Titrated Milnacipram doses
Titration to 200mg PO daily
Other Name: Savella
- Concentration of Substance P in Cerebrospinal Fluid in Response to Experiemental Pain Before and After Milnacipran Treatment. [ Time Frame: 12 weeks ]
Measure levels of Substance P present in serial samples of CSF and plasma collected over the course of 4 hours in response to application of a painful thermal stimulus at baseline ("before") and the end of 12 weeks of treatment with milnacipran 200mg daily ("after").
Substance P levels are presented. Presented data show the 10 minute and 40 minute timepoint for Substance P after pain challenge. Additional time points were not analyzed.
- Measure Sensory Threshold for Temperature Pain [ Time Frame: 12 weeks ]Investigators will utilize quantitative sensory testing to assess changes in sensory thresholds among patients with fibromyalgia before and after a twelve (12) week course of milnacipran.
- Measure Sensory Thresholds for Pressure Pain [ Time Frame: 12 weeks ]Investigator will utilize sensory testing to assess changes in sensory thresholds among patients with fibromyalgia before and after a twelve (12) week course of milnacipran.
- Measure Pain Ratings and Fibromyalgia Symptoms [ Time Frame: 12 weeks ]
Fibromyalgia patients will be asked to keep a pain diary which assess spontaneous pain ratings daily, a subjective weekly assessment, as well as degree of improvement weekly during treatment period on a numeric rating scale.
The Numeric Pain Rating Scale (NPRS) is assessing the patients pain on a 11-point rating scale from 0 - 10 with 0 corresponding to 'No Pain' and 10 corresponding to 'Worst Pain imaginable'.
- Measure Concentrations of Serotonin and Norepinephrine Cerebrospinal Fluid and Plasma [ Time Frame: 12 weeks ]
The investigators will measure cerebrospinal fluid and plasma concentrations of serotonin and norepinephrine in CSF and plasma before and after twelve (12) weeks of treatment with milnacipran.
Assays for these outcomes were not performed.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01288807
|United States, California|
|UCSD Medical Center, La Jolla|
|San Diego, California, United States, 92037|
|Principal Investigator:||Tobias Moeller-Bertram, MD, PhD, MAS||University of California, San Diego|