FibromyalgiaPhase 4ForestNCT01288807
Effect of Milnacipran on Pain in Fibromyalgia
A Phase 4 study testing Milnacipram in people with Fibromyalgia, run by University of California, San Diego at 1 site in United States.
Trial summary
The investigators want to study the effects of milnacipran treatment on neurotransmitter release in fibromyalgia. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Fibromyalgia
- What is being tested?
- Milnacipram
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2011to Jan 2015
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
UCSD Medical Center, La Jolla
San Diego, California, 92037
About this study
Official title: Effects of a 12 Week Milnacipran 200 mg Treatment on Pain Perception and Pain Processing in Fibromyalgia - An Open Label Study
The investigators want to study the effects of milnacipran treatment on neurotransmitter release in fibromyalgia.
Read the 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
- Being tested
- Milnacipram
- Keywords
- Fibromyalgia, pain
- Medical subject headings
- Fibromyalgia, Pain
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MilnacipramDrug
Also called Savella
Titration to 200mg PO daily
| Study group | Role | What they receive |
|---|---|---|
| Treatment | Experimental | Titrated Milnacipram doses Receives: Drug: Milnacipram |
What is being measured
The primary outcome is the main question the study is designed to answer.
Concentration of Substance P in Cerebrospinal Fluid in Response to Experiemental Pain Before and After Milnacipran Treatment.
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.
Measured: 12 weeks
Secondary outcomes (4)
Measure Sensory Threshold for Temperature Pain
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.
Measured: 12 weeks
Measure Sensory Thresholds for Pressure Pain
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.
Measured: 12 weeks
Measure Pain Ratings and Fibromyalgia Symptoms
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'.
Measured: 12 weeks
Measure Concentrations of Serotonin and Norepinephrine Cerebrospinal Fluid and Plasma
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.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Feb 2011 (estimated)
- Study startFeb 2011
- Primary completionJan 2015
- Study completionJan 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for FibromyalgiaStudies of the same condition, open and under way.
- More trials run by University of California, San DiegoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- Forest Laboratories, US Department of Veterans Affairs
- Responsible party
- Principal investigator, Tobias Moeller-Bertram, University of California, San Diego
- Investigators
- Tobias Moeller-Bertram, MD, PhD, MAS, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01288807
- Sponsor's protocol ID
- 100686
- Acronym
- Forest
- Status last verified
- Sep 2019
- First submitted
- 1 Feb 2011
- Last updated
- 24 Sep 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 24 Sep 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of a 12 Week Milnacipran 200 mg Treatment on Pain Perception and Pain Processing in Fibromyalgia - An Open Label Study
- ClinicalTrials.gov ID
- NCT01288807
- Acronym / sponsor ID
- Forest / 100686
- Conditions
- Fibromyalgia
- Keywords
- Fibromyalgia, pain
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- Forest Laboratories, US Department of Veterans Affairs
- Study start
- Feb 2011
- Primary completion
- Jan 2015 (actual)
- Study completion
- Jan 2015 (actual)
- First posted
- 2 Feb 2011 (estimated)
- Results
- Posted 24 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment | Experimental | Drug: MilnacipramTitrated Milnacipram doses |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MilnacipramAlso: SavellaTitration to 200mg PO daily | Drug | Treatment |
Primary outcome
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.
4 secondary outcomes
Measure Sensory Threshold for Temperature Pain
Time frame: 12 weeks
Measure Sensory Thresholds for Pressure Pain
Time frame: 12 weeks
Measure Pain Ratings and Fibromyalgia Symptoms
Time frame: 12 weeks
Measure Concentrations of Serotonin and Norepinephrine Cerebrospinal Fluid and Plasma
Time frame: 12 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Sep 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Fibromyalgia
Active, not recruiting
Objective Measurement of Pain Regulation in Individuals Who Have Received Internet-delivered Exposure-based Cognitive Behavior Therapy
Fibromyalgia
Enrolling by invitationPhase 3
Open-Label Safety Study of AXS-14 in Subjects With Fibromyalgia
Fibromyalgia
Recruiting
Exercise Interventions and Dietary Advice in Fibromyalgia and IBS
Fibromyalgia, Irritable Bowel Syndrome
Recruiting
Whole-body Cryotherapy in Those With Chronic Fatigue: A Feasibility Study
ME/CFS, Fibromyalgia (FM)
Recruiting
Auricular Acupuncture for Autonomic Balance and Pain in Fibromyalgia
Fibromyalgia Syndrome
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Tobias Moeller-Bertram, MD, PhD, MAS principal investigator
University of California, San Diego
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Milnacipram in people with Fibromyalgia, run by University of California, San Diego at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 Sep 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Concentration of Substance P in Cerebrospinal Fluid in Response to Experiemental Pain Before and After Milnacipran Treatment. (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2019.