Limiting AAA With Metformin (LIMIT) Trial

Официальное название

LIMItIng AAA With meTformin (LIMIT) Trial

Обзор

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?

Вмешательства

• Препарат Metformin
  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?
• Другое Placebo
  One group will be randomized to receive the study drug Metformin and the other group will receive a placebo

Первичные конечные точки

• 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. [Срок оценки: Baseline to 2 years]

Вторичные конечные точки (9)

• Profile of Adverse cardiovascular events [Срок оценки: Baseline to 2 years]
• Study drug compliance [Срок оценки: Baseline to 2 years]
• All-cause mortality [Срок оценки: Baseline to 2 years]
• Change in existing medication regimen as a measure of metformin treatment [Срок оценки: Baseline to 2 years]
• Change in serological markers of the liver as a measure of impact of metformin treatment [Срок оценки: Baseline to 2 years]
• Change in serological markers of the kidney as a measure of impact of metformin treatment [Срок оценки: Baseline to 2 years]
• Change in serological markers of the hematopoietic function as a measure of impact of metformin treatment [Срок оценки: Baseline to 2 years]
• Change from baseline in Living with Abdominal Aortic Aneurysm (AAA) Survey [Срок оценки: Baseline to 2 years]
• Change from baseline in Short Form (SF-36) health survey [Срок оценки: Baseline to 2 years]

Критерии участия

7.2 Inclusion Criteria

• 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.

7.3 Exclusion Criteria 1. 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

1 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Тройное слепое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Stanford Hospital and Clinics — Stanford

Идентификаторы

NCT: NCT04500756 · IRB-56500 · 1R61HL146835-01A1 · 4R33HL146835-02

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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