Metformin for Fibromyalgia

Overseen By Reiko Mitsunaga, RN

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Utah

Must not be taking: Weight controlling medications

Disqualifiers: Diabetes, Pregnancy, Cardiovascular, Autoimmune, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

72 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are using weight-controlling medications, you cannot participate in the trial.

How is the drug Metformin unique in treating fibromyalgia?

Metformin is unique in treating fibromyalgia because it is primarily used for managing blood sugar levels in diabetes, unlike the typical fibromyalgia treatments like pregabalin and duloxetine, which are used for pain and depression. This suggests a novel approach by potentially addressing fibromyalgia through metabolic pathways. ^{1 2 3 4 5}

Research Team

Akiko Okifuji, PhD

Principal Investigator

University of Utah

Norman Taylor, MD, PhD

Principal Investigator

University of Utah

Eligibility Criteria

This trial is for individuals who can follow English instructions, take oral medication, and adhere to a daily regimen. Participants must meet the criteria for Fibromyalgia Syndrome as per the American College of Rheumatology 2016. Those with diabetes, pregnancy or planning to become pregnant, serious organ diseases, autoimmune disorders, neuropathic pain, terminal illness-related pain or using weight control meds cannot join.

Inclusion Criteria

Participant must meet the American College of Rheumatology 2016 revised classification criteria for Fibromyalgia

To be able to follow the protocol in English

I can take pills and will follow a daily metformin plan.

Exclusion Criteria

I have another worsening illness as diagnosed by a doctor.

I have an autoimmune disorder like rheumatoid arthritis.

I have pain from a terminal illness or specific organ damage.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 500 mg metformin ER tablets or placebo once daily for 8 weeks

8 weeks

Weekly visits for monitoring and pill counts

Follow-up

Participants are monitored for safety and effectiveness after treatment

4-6 weeks

2 visits (in-person)

Treatment Details

Interventions

• Metformin

Trial Overview The INFORM Trial is testing if low-dose metformin improves fibromyalgia symptoms by affecting neuroinflammatory pathways. It compares the effects of metformin against a placebo in improving symptoms and altering certain cellular markers related to inflammation and pain signaling.

Participant Groups

Group I: 1: Metformin Treatment Active Control 1 Intervention

500 mg metformin ER tablets once daily in the morning with a glass of water for 8 weeks.

Group II: 2: Placebo Placebo Group 1 Intervention

Matching metformin ER placebo tablets once daily in the morning with a glass of water for 8 weeks.

Metformin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Glucophage for:

• Type 2 diabetes

Approved in United States as Glucophage for:

• Type 2 diabetes

Approved in Canada as Glucophage for:

• Type 2 diabetes

Approved in Japan as Glucophage for:

• Type 2 diabetes

Approved in China as Glucophage for:

• Type 2 diabetes

Approved in Switzerland as Glucophage for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

University of Utah

Lead Sponsor

Trials

1,169

Recruited

1,623,000+

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Collaborator

Trials

508

Recruited

1,090,000+

Findings from Research

In a 4-week clinical trial involving women with fibromyalgia, duloxetine showed a statistically significant improvement in pain scores compared to pregabalin, indicating it may be more effective for managing fibromyalgia pain.

However, the duloxetine group experienced a higher dropout rate and more nausea, suggesting that while it may be more effective, it could also have a less favorable safety profile compared to pregabalin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparing duloxetine and pregabalin for treatment of pain and depression in women with fibromyalgia: an open-label randomized clinical trial. Bidari, A., Moazen-Zadeh, E., Ghavidel-Parsa, B., et al.[2020]

In a study involving 130 fibromyalgia patients, adding palmitoylethanolamide (PEA) and acetyl-L-carnitine (ALC) to ongoing treatment with pregabalin and duloxetine led to significant improvements in pain and overall disease severity over 24 weeks.

This research is the first randomized controlled trial to show that the combination of PEA and ALC can enhance the effectiveness of standard fibromyalgia treatments, as evidenced by reduced scores on key pain and impact measures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Palmitoylethanolamide and acetyl-L-carnitine act synergistically with duloxetine and pregabalin in fibromyalgia: results of a randomised controlled study. Salaffi, F., Farah, S., Sarzi-Puttini, P., et al.[2023]

Fibromyalgia syndrome (FMS) affects 1-5% of the population and is characterized by neural oversensitization and cognitive dysfunction, making its treatment complex; currently, only three drugs (pregabalin, duloxetine, and milnacipran) are FDA-approved for its management.

Future research into cannabinoids, opioids, and personalized medicine approaches, including genetics and functional imaging, may lead to the development of more effective and tailored treatments for FMS patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current and Emerging Pharmacotherapy for Fibromyalgia. Tzadok, R., Ablin, JN.[2020]

A study on fibromyalgia treatments found that 82% of patients were prescribed only one medication, with pregabalin and duloxetine being the most common choices, used by 21% and 20% of patients respectively.

The majority of treatments were from the antidepressant class (46%), followed by antiepileptics (35%) and pain therapies (25%), indicating a diverse approach to managing fibromyalgia symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of fibromyalgia. Dussias, P., Kalali, AH., Staud, RM.[2021]

Pregabalin (Lyrica) is the first approved medication for managing fibromyalgia syndrome (FMS) and has been shown to effectively reduce pain, improve sleep, and enhance quality of life in FMS patients based on five randomized, placebo-controlled trials.

While pregabalin is generally safe and can be combined with other medications, it may cause side effects like somnolence and dizziness, and should be started at a low dose (25-50 mg) to minimize these effects, with careful monitoring for any worsening of depression or suicidal thoughts.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pregabalin for the management of fibromyalgia syndrome. Boomershine, CS.[2021]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Comparing duloxetine and pregabalin for treatment of pain and depression in women with fibromyalgia: an open-label randomized clinical trial. [2020]

2. Italy pubmed.ncbi.nlm.nih.gov

Palmitoylethanolamide and acetyl-L-carnitine act synergistically with duloxetine and pregabalin in fibromyalgia: results of a randomised controlled study. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

Current and Emerging Pharmacotherapy for Fibromyalgia. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Treatment of fibromyalgia. [2021]

5. New Zealand pubmed.ncbi.nlm.nih.gov

Pregabalin for the management of fibromyalgia syndrome. [2021]