Metformin for Immune Dysregulation in Drug Users

((MET-IH) Trial)

Overseen By Dr. Kobie

Age: 18 - 65

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Alabama at Birmingham

Must not be taking: Metformin, Diabetes medications, Furosemide, others

Disqualifiers: Diabetes, Renal impairment, Liver disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 16 weeks

100 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether metformin, a medication commonly used for diabetes, can reduce inflammation and improve immune function in individuals who have used injection drugs. Participants will take either metformin or a placebo (a harmless pill without active medication) to assess immune system responses, including vaccine efficacy. Suitable candidates for this trial include those who have injected opioids, amphetamines, or cocaine within the last 10 years and are willing to receive specific vaccines. As a Phase 4 trial, this research aims to understand how an already FDA-approved and effective treatment can benefit more patients.

Do I have to stop taking my current medications for the trial?

The trial requires that you stop taking metformin or other diabetes medications, as well as certain other medications like furosemide, nifedipine, ranolazine, vandetanib, or cimetidine if you are currently using them or have used them in the past 30 days.

What is the safety track record for this treatment?

Research has shown that metformin is usually safe for use. This well-known drug often treats type 2 diabetes. Studies have found that metformin can help reduce inflammation, which might benefit conditions related to inflammation.

Serious side effects are rare. Some individuals might experience mild issues like nausea or diarrhea initially, but these often improve over time. Additionally, since this trial is in a later stage, substantial evidence already supports its safety. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Metformin is unique because it targets immune dysregulation, which is not its traditional use. Typically known for treating diabetes, Metformin is being explored for its potential to restore immune function and reduce inflammation in drug users. This is exciting because it could offer a new way to support immune health in a population with few targeted options, possibly leading to broader applications beyond its current use. Researchers are keen to see if this repurposed approach can deliver significant health benefits in a relatively short time frame.

What evidence suggests that metformin might be an effective treatment for immune dysregulation in drug users?

Research has shown that metformin, which participants in this trial may receive, can help reduce inflammation, a significant issue in immune system disorders. Studies have found that metformin lowers inflammation markers like TNF-α, often elevated in individuals with immune problems. In conditions like diabetes, where immune issues are common, metformin has improved immune system function. Additionally, metformin reduced lung inflammation in animal studies, suggesting broader anti-inflammatory benefits. Based on these findings, this trial will assess whether metformin may improve immune function in people with a history of injection drug use. ^{1 2 6 7 8}

Are You a Good Fit for This Trial?

This trial is for people who have used injection drugs and may or may not be living with HIV. It's designed to see if metformin can help reduce inflammation and improve their immune systems.

Inclusion Criteria

I have been on HIV medication for more than a year.

I am willing and able to follow the study rules and attend all required visits.

History of injection opioid, amphetamine, and/or cocaine use within the past 10 years (self-report)

Exclusion Criteria

I have had metabolic acidosis before.

I am unable to understand and give consent for treatment.

Pregnant or nursing individuals

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Metformin or placebo for 16 weeks, with immune system assessments and vaccine administration

16 weeks

Regular visits for assessments and vaccine administration

Follow-up

Participants are monitored for immune response and safety after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Metformin

Trial Overview The study tests metformin against a placebo in reducing systemic inflammation and boosting immune function. Participants will also receive vaccines, Capvaxvie or Jynneos, to assess vaccine response as part of the immune evaluation.

How Is the Trial Designed?

Group I: Metformin Group Experimental Treatment 3 Interventions

Participants will receive Metformin ER (500mg increasing to 1000mg) for 16 weeks to assess immune restoration and inflammatory response.

Group II: Placebo Group Placebo Group 3 Interventions

Control Group

Who Is Running the Clinical Trial?

University of Alabama at Birmingham

Lead Sponsor

Trials

1,677

Recruited

2,458,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11965306/

Metformin alleviates inflammatory response and severity ... Our result suggest that MET treatment reduces the severity rate of Covid-19 infection by alleviating inflammatory response through decreasing ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10680465/

The Role and Mechanism of Metformin in Inflammatory Diseases As shown in a mouse model, metformin significantly reduced lung inflammation in SiO2-instilled mice at the fibrotic stages, which can be exacerbated by ...

3. nature.com nature.com/articles/s41598-022-09639-2

Metformin is associated with favorable outcomes in ... In the present study, we aimed to address whether metformin use is beneficial in COVID-19 patients with pre-existing type 2 diabetes mellitus.

4. sciencedirect.com sciencedirect.com/science/article/pii/S2772431X25000504

Immune dysregulation in type 2 diabetes mellitus This not only affects treatment effectiveness but also raises the risk of drug resistance, a serious public health concern in TB therapy.

5. joe.bioscientifica.com joe.bioscientifica.com/view/journals/joe/251/2/JOE-21-0194.xml

Metformin as an anti-inflammatory agent: a short review in With glycaemic levels being similar in both groups, metformin led to significantly lower levels of TNF-α and sICAM-1, but not CRP or IL-6 (Lund et al. 2008).

6. sciencedirect.com sciencedirect.com/science/article/pii/S2589004223021594

Metformin inhibits inflammatory response and endoplasmic ... Metformin alleviates ER stress in hypothalamic neurons of obese mice. ER stress is linked with aging and neurodegenerative diseases. Therefore, ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06829238

Study Details | NCT06829238 | Assessment of Metformin ... This randomized clinical trial (RCT) evaluates whether metformin can reduce systemic inflammation and improve immune function in individuals with a history of ...

8. frontiersin.org frontiersin.org/journals/immunology/articles/10.3389/fimmu.2018.01236/full

Metformin and Autoimmunity: A “New Deal” of an Old Drug Studies suggest that metformin interferes with key immunopathological mechanisms involved in systemic autoimmune diseases.