Clinical trial NCT01288807: Effect of Milnacipran on Pain in Fibromyalgia
Official title: Effects of a 12 Week Milnacipran 200 mg Treatment on Pain Perception and Pain Processing in Fibromyalgia - An Open Label Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Fibromyalgia
Keywords: Fibromyalgia
pain
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: Forest Laboratories
name: US Department of Veterans Affairs
First posted: 2011-02-02
Enrollment: 8
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The investigators want to study the effects of milnacipran treatment on neurotransmitter release in fibromyalgia.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* Female age 18 or older
* Written informed consent and written release of health and research study information
* Diagnosis of Fibromyalgia
* Participant has pain greater than 4 on the NRS of 0 to 10 on average over the last week prior to initial evaluation that interferes with function most days per week
* Pain duration greater than 6 months
* Negative urine pregnancy test on experimental day 1 and 2 and on first day of treatment prior to administration of study medication and fluoroscopy
* Ability to speak and understand English, to follow instructions, and fill out study questionnaires
* Likely to complete all required visits
* Must be ambulatory and able to lay prone for 30 minutes

Exclusion Criteria:

* Any condition or situation that in the investigator's opinion may put the participant at significant risk, confound the study results, or interfere significantly with the participant's participation in the study
* Serious, unstable medical illness that could lead to hospitalization over the next three months; and/or a DSM-IV diagnosis(es) with active problems within the last six months, such as: schizophrenia, bipolar disorder, antisocial personality disorder, or substance use disorder
* Known, uncontrolled, serious systemic disease, including: hypertension and/or tachyarrythmia
* Females who are pregnant, breast feeding, or who plan to become pregnant, or who may potentially become pregnant
* Allergy or sensitivity to any component of the study medication or to contrast dye
* Patients on coumadin, heparin, or any other known increase risk of bleeding
* Signs of increased intracranial pressure
* Patients who are unable to continue current pain medication
* Allergy or contraindication to acetaminophen
* Use of monoamine oxidase inhibitors
* Uncontrolled narrow-angle glaucoma

Primary outcomes:
measure: Concentration of Substance P in Cerebrospinal Fluid in Response to Experiemental Pain Before and After Milnacipran Treatment.
timeFrame: 12 weeks
Secondary outcomes:
measure: Measure Sensory Threshold for Temperature Pain
timeFrame: 12 weeks
measure: Measure Sensory Thresholds for Pressure Pain
timeFrame: 12 weeks
measure: Measure Pain Ratings and Fibromyalgia Symptoms
timeFrame: 12 weeks
measure: Measure Concentrations of Serotonin and Norepinephrine Cerebrospinal Fluid and Plasma
timeFrame: 12 weeks
Other outcomes:
Locations:
city: San Diego
country: United States
facility: UCSD Medical Center, La Jolla
state: California
Study officials:
affiliation: University of California, San Diego
name: Tobias Moeller-Bertram, MD, PhD, MAS
role: PRINCIPAL_INVESTIGATOR
References: