Effect of Milnacipran on Pain in Fibromyalgia

NCT ID: NCT01288807

Last Updated: 2019-09-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 8 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-02-28
• Study Completion Date: 2015-01-31

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.

Conditions

Fibromyalgia

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment

Titrated Milnacipram doses

Group Type: EXPERIMENTAL

Milnacipram

Intervention Type: DRUG

Titration to 200mg PO daily

Interventions

Milnacipram

Titration to 200mg PO daily

Intervention Type: DRUG

Other Intervention Names

Savella

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Forest Laboratories

INDUSTRY

Sponsor Role: collaborator

US Department of Veterans Affairs

FED

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Tobias Moeller-Bertram

MD, PhD, MAS Associate Clinical Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Tobias Moeller-Bertram, MD, PhD, MAS

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Locations

UCSD Medical Center, La Jolla

San Diego, California, United States

Countries

United States

Other Identifiers

100686

Identifier Type: -

Identifier Source: org_study_id