Fibromyalgia SyndromePhase 2NCT05900466
Metformin for Fibromyalgia Symptoms (INFORM Trial)
A Phase 2 study testing Metformin in people with Fibromyalgia Syndrome, run by University of Utah at 1 site in United States.
Trial summary
The main purpose of the project is to evaluate the safety and efficacy of low dose metformin for improving symptoms associated with fibromyalgia syndrome (FMS) via modulating neuroinflammatory pathways. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Fibromyalgia Syndrome
- What is being tested?
- Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Apr 2023to 31 Mar 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- To be able to follow the protocol in English
- Fibromyalgia Syndrome: Participant must meet the American College of Rheumatology 2016 revised classification criteria for Fibromyalgia
- Ability to take oral medication and be willing to adhere to the metformin regimen (once daily)
Who cannot join
- Co-occurring progressive disease (self-report, physician-diagnosed)
- Diabetes
- Pregnancy or planning to be pregnant in the next year (all premenopausal participants will be tested)
- Having known cardiovascular, liver, kidney or pulmonary diseases (self-report, physician-diagnosed)
- Having known serious psychopathology (Clinician diagnoses of psychosis, organic mental disorder, or dissociative disorder, self-reported active suicidal intent, self-reported history of inpatient admission to a psychiatric ward in the past year, evidence or self-report of self-injurious behaviors in the past year, reported current or recent history (2years) of non-IV substance abuse, any history of recreational IV drug use)
- Having autoimmune disorder (e.g., rheumatoid arthritis) (self-report, physician-diagnosed)
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- Having neuropathic pain (self-report, physician-diagnosed)
- Having pain associated with a terminal illness, acute pain, pain associated with specific organ damage (eg, stomach ulcer) (self-report, physician-diagnosed)
- Concurrent use of weight controlling medications (eg, Xenical)
- Requiring an interpreter to communicate
- Abnormal levels of creatinine, vitamin B12, or hepatic function panel
- eGFR of below 45mL/min/1.73m2
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Utah
Salt Lake City, Utah, 84132
Reiko Mitsunaga, RN, 801-585-7695, reiko.mitsunaga@hsc.utah.edu
About this study
Official title: Metformin as a Novel, Mechanistic Treatment of Fibromyalgia; a Proof of Concept RCT
The main purpose of the project is to evaluate the safety and efficacy of low dose metformin for improving symptoms associated with fibromyalgia syndrome (FMS) via modulating neuroinflammatory pathways. The investigators hypothesize that FMS patients in the low-dose metformin conditions will show greater improvement in FMS symptoms than those who are in the placebo group. Further, the investigators hypothesize that metformin will increase phosphorylated AMPK in peripheral immune cells of FMS patients and will decrease the transcription of mTORC1, NLRP3 inflammasome, and nociceptive cytokines interleukin 1beta and interleukin 18.
Read the detailed description
Fibromyalgia syndrome (FMS) is a chronic pain condition that is debilitating to an estimated 10 million Americans and results in high utilization of medical resources with a cost of over $100 billion in health care and lost productivity each year. It is widely accepted that chronic widespread pain is a defining feature of FMS and that it is maintained by central sensitization. Accumulating evidence demonstrates that central sensitization is driven, at least in part, by neuroinflammation. Thus, molecules that ameliorate the causes of neuroinflammation are intriguing candidates to treat FMS symptoms. Current therapies are only partially effective in about 50% of patients. The development of a treatment approach with better efficacy is urgently needed.
The investigators propose to test the use of metformin for FMS. This drug is widely used as a first line treatment for type II diabetes. Metformin causes the phosphorylation of AMP-activated protein kinase (AMPK), which regulates key enzymes and transcription factors that modulate gene expression involved in metabolism and inflammation. Because AMPK acts as a master switch kinase, this target may prove particularly effective in treating the many diverse symptoms of FMS. Indeed, metformin treated hyperalgesia in preclinical models of neuropathic, inflammatory, spinal cord injury and diabetes-induced mechanical hyperalgesia and reduced symptoms of anxiety, depression and cognitive dysfunction. This is of significant relevance because these symptoms contribute greatly to FMS patient disability.
The investigators expect that this study will determine the effectiveness of metformin on pain and comorbidity FMS symptoms and delineate the role that AMPK and its downstream targets play on these phenotypes. The investigators anticipate that these results will demonstrate the efficacy of an intervention not currently used clinically to treat FMS. Understanding these pathways represents a critical step in the development of non-addictive pain treatments and holds enormous potential to reduce disability in the 10 million Americans with FMS.
- Conditions
- Fibromyalgia Syndrome
- Being tested
- Metformin, Placebo
- Keywords
- FMS
- Medical subject headings
- Fibromyalgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Glucophage XR (metformin hydrochloride), Glucophage (metformin hydrochloride)
500 mg Metformin ER tablets once daily in the morning for 8 weeks
PlaceboDrug
Matching tablets once daily in the morning for 8 weeks
| Study group | Role | What they receive |
|---|---|---|
| 1: Metformin Treatment | Active comparator | 500 mg metformin ER tablets once daily in the morning with a glass of water for 8 weeks. Receives: Drug: Metformin |
| 2: Placebo | Placebo comparator | Matching metformin ER placebo tablets once daily in the morning with a glass of water for 8 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the safety and efficacy of low-dose metformin in improving the symptoms associated with FMS
Safety will be measured by the Fibromyalgia Impact Questionnaire, Revised (FIQ-R score and will measure overall FMS severity. The numeric scale ranges from 0-10 with 0 being "low difficulty" (better outcome) and 10 being "high difficulty" (worse outcome).
Measured: 12-14 weeks
Secondary outcomes (10)
Examine changes in individual FMS symptoms - Pain Intensity
Efficacy will be evaluated for a range of symptoms through the PROMIS Short Form measures of pain intensity (PROMIS Pain Intensity SF3a). The scale ranges from 0-10, 0 being "no pain" (better outcome) and 10 being "worst pain imaginable" (worse outcome).
Measured: 12-14 weeks
Examine changes in individual FMS symptoms - Fatigue
Efficacy will be evaluated for a range of symptoms through the PROMIS Short Form measures of fatigue (PROMIS Fatigue SF7a). The scale ranges from 1-5, 1 being "not at all" (better outcome) and 5 being "very much" (worse outcome).
Measured: 12-14 weeks
Examine changes in individual FMS symptoms - Sleep Disturbance
Efficacy will be evaluated for a range of symptoms through the PROMIS Short Form measures of sleep disturbance (PROMIS Sleep Disturbance SF8b). The scale ranges from 1-5, 1 being "very poor" or "not at all" (worse outcome) and 5 being "very good" or "very much" (better outcome).
Measured: 12-14 weeks
Examine changes in individual FMS symptoms - Depression
Efficacy will be evaluated for a range of symptoms through the PROMIS Short Form measures of depression (PROMIS Depression SF8b). The scale ranges from 1-5, 1 being "never" (better outcome) and 5 being "always" (worse outcome).
Measured: 12-14 weeks
Examine changes in individual FMS symptoms - Anxiety
Efficacy will be evaluated for a range of symptoms through the PROMIS Short Form measures of anxiety (PROMIS Anxiety SF7a). The scale ranges from 1-5, 1 being "never" (better outcome) and 5 being "always" (worse outcome).
Measured: 12-14 weeks
Examine changes in individual FMS symptoms - Physical Function
Efficacy will be evaluated for a range of symptoms through the PROMIS Short Form measures of physical functioning (PROMIS Physical Function SF10a). The scale ranges from 1-5, 1 being "unable to do" (worse outcome) and 5 being "without any difficulty" (better outcome).
Measured: 12-14 weeks
Examine changes in individual FMS symptoms - Perceived Cognitive Function
Efficacy will be evaluated for a range of symptoms through the PROMIS Short Form measures of perceived cognitive functioning (title: Multiple Ability Self-Report Questionnaire (MASQ)). The scale ranges from 1-5 with 1 being "never" (better outcome) to 5 being "always" (worse outcome).
Measured: 12-14 weeks
Examine changes in ecological momentary assessment (EMA) symptoms
EMA will allow us to evaluate symptom variations at home environment
Measured: 12-14 weeks
Examine patient's global improvement impression
Global impression of improvement scale will be used to assess clinical global impression (CGI). Global impression of improvement scale is a 7-point scale. Scores range from 1 being the better outcome (i.e. "normal", "improved") and 7 being the worse outcome (i.e. "most severely ill", "very much worse").
Measured: 12-14 weeks
Examine adherence
Pill counts will provide us with a measure of adherence
Measured: Week 4 and week 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2023
- Study start1 Apr 2023
- Primary completion31 Mar 2027 (estimated)
- Study completion31 Mar 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Fibromyalgia SyndromeStudies of the same condition, open and under way.
- More trials run by University of UtahThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- We will conduct a proof of concept pilot study, a single site, randomized, double-blinded, phase 2 clinical trial with 2 parallel dosing arms comparing the effects of placebo, and 500mg of once a day metformin on improving hyperalgesia and other symptoms in 72 patients with FMS.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Responsible party
- Sponsor
- Investigators
- Akiko Okifuji, PhD, Principal investigator, University of UtahNorman Taylor, MD, PhD, Principal investigator, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05900466
- Sponsor's protocol ID
- 00160543
- Other IDs
- R21AR082574
- Status last verified
- Mar 2026
- First submitted
- 17 May 2023
- Last updated
- 30 Mar 2026
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Metformin as a Novel, Mechanistic Treatment of Fibromyalgia; a Proof of Concept RCT
- ClinicalTrials.gov ID
- NCT05900466
- Acronym / sponsor ID
- 00160543
- Conditions
- Fibromyalgia Syndrome
- Keywords
- FMS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Study start
- 1 Apr 2023 (actual)
- Primary completion
- 31 Mar 2027 (estimated)
- Study completion
- 31 Mar 2027 (estimated)
- First posted
- 12 Jun 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main purpose of the project is to evaluate the safety and efficacy of low dose metformin for improving symptoms associated with fibromyalgia syndrome (FMS) via modulating neuroinflammatory pathways. The investigators hypothesize that FMS patients in the low-dose metformin conditions will show greater improvement in FMS symptoms than those who are in the placebo group. Further, the investigators hypothesize that metformin will increase phosphorylated AMPK in peripheral immune cells of FMS patients and will decrease the transcription of mTORC1, NLRP3 inflammasome, and nociceptive cytokines interleukin 1beta and interleukin 18.
Detailed description
Fibromyalgia syndrome (FMS) is a chronic pain condition that is debilitating to an estimated 10 million Americans and results in high utilization of medical resources with a cost of over $100 billion in health care and lost productivity each year. It is widely accepted that chronic widespread pain is a defining feature of FMS and that it is maintained by central sensitization. Accumulating evidence demonstrates that central sensitization is driven, at least in part, by neuroinflammation. Thus, molecules that ameliorate the causes of neuroinflammation are intriguing candidates to treat FMS symptoms. Current therapies are only partially effective in about 50% of patients. The development of a treatment approach with better efficacy is urgently needed.
The investigators propose to test the use of metformin for FMS. This drug is widely used as a first line treatment for type II diabetes. Metformin causes the phosphorylation of AMP-activated protein kinase (AMPK), which regulates key enzymes and transcription factors that modulate gene expression involved in metabolism and inflammation. Because AMPK acts as a master switch kinase, this target may prove particularly effective in treating the many diverse symptoms of FMS. Indeed, metformin treated hyperalgesia in preclinical models of neuropathic, inflammatory, spinal cord injury and diabetes-induced mechanical hyperalgesia and reduced symptoms of anxiety, depression and cognitive dysfunction. This is of significant relevance because these symptoms contribute greatly to FMS patient disability.
The investigators expect that this study will determine the effectiveness of metformin on pain and comorbidity FMS symptoms and delineate the role that AMPK and its downstream targets play on these phenotypes. The investigators anticipate that these results will demonstrate the efficacy of an intervention not currently used clinically to treat FMS. Understanding these pathways represents a critical step in the development of non-addictive pain treatments and holds enormous potential to reduce disability in the 10 million Americans with FMS.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- We will conduct a proof of concept pilot study, a single site, randomized, double-blinded, phase 2 clinical trial with 2 parallel dosing arms comparing the effects of placebo, and 500mg of once a day metformin on improving hyperalgesia and other symptoms in 72 patients with FMS.
| Arm | Type | Receives |
|---|---|---|
| 1: Metformin Treatment | Active comparator | Drug: Metformin500 mg metformin ER tablets once daily in the morning with a glass of water for 8 weeks. |
| 2: Placebo | Placebo comparator | Drug: PlaceboMatching metformin ER placebo tablets once daily in the morning with a glass of water for 8 weeks. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- To be able to follow the protocol in English
- Fibromyalgia Syndrome: Participant must meet the American College of Rheumatology 2016 revised classification criteria for Fibromyalgia
- Ability to take oral medication and be willing to adhere to the metformin regimen (once daily)
Key exclusion criteria (12 listed)
- Co-occurring progressive disease (self-report, physician-diagnosed)
- Diabetes
- Pregnancy or planning to be pregnant in the next year (all premenopausal participants will be tested)
- Having known cardiovascular, liver, kidney or pulmonary diseases (self-report, physician-diagnosed)
- Having known serious psychopathology (Clinician diagnoses of psychosis, organic mental disorder, or dissociative disorder, self-reported active suicidal intent, self-reported history of inpatient admission to a psychiatric ward in the past year, evidence or self-report of self-injurious behaviors in the past year, reported current or recent history (2years) of non-IV substance abuse, any history of recreational IV drug use)
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 |
|---|---|---|
| MetforminAlso: Glucophage XR (metformin hydrochloride), Glucophage (metformin hydrochloride)500 mg Metformin ER tablets once daily in the morning for 8 weeks | Drug | 1: Metformin Treatment |
| PlaceboMatching tablets once daily in the morning for 8 weeks | Drug | 2: Placebo |
Primary outcome
Evaluate the safety and efficacy of low-dose metformin in improving the symptoms associated with FMS
Time frame: 12-14 weeks
Safety will be measured by the Fibromyalgia Impact Questionnaire, Revised (FIQ-R score and will measure overall FMS severity. The numeric scale ranges from 0-10 with 0 being "low difficulty" (better outcome) and 10 being "high difficulty" (worse outcome).
10 secondary outcomes
Examine changes in individual FMS symptoms - Pain Intensity
Time frame: 12-14 weeks
Examine changes in individual FMS symptoms - Fatigue
Time frame: 12-14 weeks
Examine changes in individual FMS symptoms - Sleep Disturbance
Time frame: 12-14 weeks
Examine changes in individual FMS symptoms - Depression
Time frame: 12-14 weeks
Examine changes in individual FMS symptoms - Anxiety
Time frame: 12-14 weeks
Examine changes in individual FMS symptoms - Physical Function
Time frame: 12-14 weeks
Examine changes in individual FMS symptoms - Perceived Cognitive Function
Time frame: 12-14 weeks
Examine changes in ecological momentary assessment (EMA) symptoms
Time frame: 12-14 weeks
Examine patient's global improvement impression
Time frame: 12-14 weeks
Examine adherence
Time frame: Week 4 and week 14
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2026.
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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.
Akiko Okifuji, PhD principal investigator
University of Utah
Norman Taylor, MD, PhD principal investigator
University of Utah
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin in people with Fibromyalgia Syndrome, run by University of Utah 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 3 inclusion and 12 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: looking for participants now, as of the sponsor's last update on 30 Mar 2026. 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. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Reiko Mitsunaga, RN (801-585-7695, reiko.mitsunaga@hsc.utah.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate the safety and efficacy of low-dose metformin in improving the symptoms associated with FMS (time frame: 12-14 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 30 Mar 2026.