Limiting AAA With Metformin (LIMIT) Trial
ConditionAbdominal Aortic Aneurysm
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age50-95
SponsorStanford University
About this trial
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?
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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;
Disqualifiers
Diagnosis of, or taking medications for, diabetes mellitus, as defined as HgbA1c > 6.5% at baseline evaluation; 2. Known hypersensitivity to metformin hydrochloride. Individuals with known prior anaphylactic reaction to iodinated contrast will have the option of CT scan without contrast or will not be eligible to participate. Individuals with a prior allergic reaction not including anaphylaxis will be managed with the standard CT protocol for premedication for allergy to contrast - 3 doses of prednisone (50 mg p.o. per) beginning 13 hours prior to the procedure as well as 50 mg of Benadryl p.o. Premedication start times are as follows: 13 hours before contrast, 50 mg PO prednisone 7 hours before contrast, 50 mg PO prednisone
Trial design
Design model
Parallel
Treatments tested in this trial
Metformin
DrugSmaller 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?
Placebo
Other interventionOne group will be randomized to receive the study drug Metformin and the other group will receive a placebo
Treatment groups
314 Participants
are divided into 2 treatment groupsGroup A: Metformin groupActive comparator 1 intervention
Group B: Placebo GroupPlacebo comparator 1 intervention
Trial outcomes
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.
Time frame
Baseline to 2 yearsSecondary outcomes
1
Profile of Adverse cardiovascular events
Incidence of adverse cardiovascular events including: unanticipated adverse events (AEs) and serious AEs (SAEs), AEs leading to premature discontinuation from the study intervention and serious treatment-emergent AEs, clinically significant AE events, such as cardiovascular AEs and surgical AAA repairs.
Time frame
Baseline to 2 years2
Study drug compliance
Pill counts will be used to measure study drug compliance.
Time frame
Baseline to 2 years3
All-cause mortality
All-cause mortality will be summarized using Kaplan-Meier survival curves for each arm. Participants alive at last follow-up will be censored at last time known alive.
Time frame
Baseline to 2 years4
Change in existing medication regimen as a measure of metformin treatment
Concurrent medication regimen will be tabulated and listed according to the drug classifications
Time frame
Baseline to 2 yearsSponsors and contacts
Click on the lead sponsor to view all of their trials.
Stanford University
Lead sponsor
Kaiser Permanente
Collaborator
VA Palo Alto Health Care System
Collaborator
National Heart, Lung, and Blood Institute (NHLBI)
Collaborator
Source ClinicalTrials.gov