Limiting AAA With Metformin (LIMIT) Trial

NCT04500756 | Recruiting Phase 2 DMC FDA Drug

• 3 other identifiers: IRB-565001R61HL146835-01A14R33HL146835-02
• Study Type: interventional
• Target: 314
• Locations: 1 country
• Sites: 1

Brief Summary

In this research, the investigators are looking at the effects of a drug called metformin may have on the growth of abdominal aortic aneurysm (AAA)s. AAA is an abnormal enlargement of the aorta, which is the large artery in the abdomen (stomach area). The enlargement of the aorta carries a risk that it will rupture and cause life-threatening bleeding in the abdomen (belly). In this study the investigators hope to learn how metformin is associated with the enlargement or change in size of the AAA in study participants. Smaller studies have suggested that metformin may reduce the rate at which aortic aneurysms enlarge. This study will test this question: does metformin prevent AAAs from growing larger?

Conditions

Abdominal Aortic Aneurysm

Outcome Measures

Primary Outcomes (1)

• The primary outcome measure will be the change in maximal orthogonal diameter of the infrarenal aorta, as measured by computed tomographic (CT) aortography, in centimeters.

  The change in maximal orthogonal diameter of the infrarenal aorta, as measured by computed tomographic (CT) aortography, over the course of the study in participants taking metformin XR (extended release) vs. placebo. It is calculated as the difference in CTA-determined diameter (in mm) from baseline to the follow-up CT study at the end of study participation, divided by time elapsed between two measurements (e.g., annual rate of change in CT-diameter). The justification for this endpoint is that maximal orthogonal transverse diameter by CTA is the primary standard to measure AAA disease progression, determine need for surgical intervention, and correlate with clinical outcomes.

  Baseline to 2 years

Secondary Outcomes (9)

• Profile of Adverse cardiovascular events

  Baseline to 2 years

• Study drug compliance

  Baseline to 2 years

• All-cause mortality

  Baseline to 2 years

• Change in existing medication regimen as a measure of metformin treatment

  Baseline to 2 years

• Change in serological markers of the liver as a measure of impact of metformin treatment

  Baseline to 2 years

Study Arms (2)

Metformin group

ACTIVE COMPARATOR

Participants will either be assigned to take metformin 500 mg tablet(s) daily or identical tablet(s) that contain no active drug, also taken every day. Over the first four weeks of the study, you will increase your dosage every week by one pill, so at the end of the first month you will be taking up to four pills per day. If you develop any symptoms or side effects from pill ingestion during this process, your dose will be decreased to the last number of pills you were able to take without developing side effects.

Drug: Metformin

Placebo Group

PLACEBO COMPARATOR

Participants will either be assigned to take metformin 500 mg tablet(s) daily or identical tablet(s) that contain no active drug, also taken every day. Over the first four weeks of the study, you will increase your dosage every week by one pill, so at the end of the first month you will be taking up to four pills per day. If you develop any symptoms or side effects from pill ingestion during this process, your dose will be decreased to the last number of pills you were able to take without developing side effects.

Other: Placebo

Interventions

Metformin DRUG

Smaller studies have suggested that metformin may reduce the rate at which aortic aneurysms enlarge. This study will test this question: does metformin prevent AAAs from growing larger?

Also known as: AAA

Metformin group

Placebo OTHER

One group will be randomized to receive the study drug Metformin and the other group will receive a placebo

Placebo Group

Eligibility Criteria

• Age: 50 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent;
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 50 to 95 years inclusive;
• Have a maximal orthogonal infrarenal aortic diameter between 35 and \< 50 mm for males and between 30 and \< 45 mm for females as measured by CTA;
• Eligible participants must have an estimated glomerular filtration rate (eGFR) of ≥ 30 ml/min/1.73 m2 at the initiation of trial participation, and must remain ≥ 30 ml/min/1.73 m2 throughout the term of the study to continue participation;
• HgbA1c must be ≤ 6.5% at initiation to receive study medication;
• Ability to take oral medication and be willing to adhere to the medication regimen throughout the course of the trial;
• Must be willing and able to undergo two computed tomographic aortograms (CTA, with timed intravenous iodinated contrast injections if possible) at initiation and termination of study participation;
• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening, with an agreement to use such a method of contraception during study participation and for an additional 4 weeks after the end of study drug administration.

You may not qualify if:

• hour before contrast, 50 mg PO prednisone + 50 mg PO diphenhydramine These individuals will also be given the option of CT scan without contrast if unwilling to follow the premedication as indicated above; 3. Presence of metabolic acidosis, defined as total CO2 below the lower limit of normal on chemistry panel obtained during determination of study eligibility; 4. Expected survival less than two years; 5. Prior surgical AAA repair, or anticipated repair within two years; 6. Known thoracic aortic aneurysm disease, as defined as a prior dissection or thoracic aortic diameter \> 5 cm); 7. The presence of known syndromic aortic conditions, including but not limited to Ehlers Danlos or Marfan Syndromes, or the at-risk allele in the ACTA2 gene mutation or similar conditions; 8. Severe liver disease, jaundice, or active hepatitis; 9. Severe anemia, defined as a Hgb \< 10g/dl; 10. Concurrent participation in other investigational drug trials; 11. For female participants of childbearing potential: pregnancy, intent to become pregnant, lactation, or unwilling or unable to use an effective method of contraception; 12. Alcoholism or chronic excessive alcohol intake; 13. Common iliac artery aneurysms \> 3.5 cm; 14. Uncontrolled hypertension defined as Systolic BP≥200, or considered to have hypertensive emergency or urgency.

Sponsors & Collaborators

• Stanford University: lead
• Kaiser Permanente: collaborator
• VA Palo Alto Health Care System: collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Stanford Hospital and Clinics

Stanford, California, 94305, United States

RECRUITING

MeSH Terms

Conditions

Aortic Aneurysm, Abdominal

Interventions

Metformin

Condition Hierarchy (Ancestors)

Aortic Aneurysm; Aneurysm; Vascular Diseases; Cardiovascular Diseases; Aortic Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Ronald Dalman, MD

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sohrab Sami

CONTACT

412-452-7137; ssami@stanford.edu

Ronald Dalman, MD

CONTACT

650-725-5227; rld@stanford.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: randomized (which means assigned by chance, like flipping a coin) into one of two groups. You will either be assigned to take metformin 500 mg tablet(s) daily or identical tablet(s) that contain no active drug, also taken every day.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Division Chief of Stanford Vascular Surgery

Model Details: Prospective, randomized, controlled trial comparing the ability of metformin to prevent AAA disease progression vs. placebo.

Study Record Dates

• First Submitted: June 6, 2020
• First Posted: August 5, 2020
• Study Start: February 28, 2022
• Primary Completion (Estimated): June 30, 2028
• Study Completion (Estimated): June 30, 2028
• Last Updated: April 18, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)