Alpha-Ketoglutarate and Abdominal Aortic Aneurysm Progression and Rupture

Abdominal aortic aneurysm (AAA) is an age-related disease that characterized by permanent regional dilation of the abdominal aortae, which results in catastrophic event of rupture and sudden death. Currently, no effective drug to limit the progression or reduce the risk of rupture has been developed.

Metabolic pathways, including glucose metabolism, lipid metabolism, and amino acid metabolism, have indispensable roles in normal and dysfunctional vasculature. The Krebs cycle is responsible for obtaining energy from food in the form of ATP, and ATP is essential for muscle contraction and correct functioning of all organs. Besides, tight control of mitochondrial functions is critical for maintaining metabolism balance.

As an important metabolite in Krebs cycle, alpha-ketoglutarate not only improved energy metabolism, but also extended lifespan and reduced morbidity in aging mice. It is widely used in the market as a nutritional supplement specially by athletes to increase muscle strength. Until now, no obvious toxic and side effects to the body was observed. Given the high bioavailability, we propose that dietary supplementation with alpha-ketoglutarate can improve the outcome in patients with an abdominal aortic aneurysm of 39-49 mm in diameter.

Therefore, the project team intends to establish the abdominal aortic aneurysm rupture risk prediction model in the elderly cohort in the early stage, and randomize groups in patients with an abdominal aortic aneurysm of 39-49 mm in diameter based on whether or not to supplement alpha-ketoglutarate. There are two cohorts: the alpha-ketoglutarate intervention cohort and the parallel control cohort. By observing the efficacy in terms of change in aortic diameter and abdominal aortic aneurysm rupture incidence in the two groups during the follow-up period, it provides evidence-based medical evidence for the future clinical application of alpha-ketoglutarate.

Inclusion criteria

• Presence of an infrarenal AAA with a maximum diameter of 39-49 mm;
• Han nationality;
• Between 50 years or more, no gender limit;
• No mental illness;
• No history of supplement allergy or supplement allergy;
• Subjects voluntarily participate in this study, sign an informed consent form, have good compliance, and cooperate with follow-up.

Exclusion criteria

• Previous infrarenal aortic surgery;
• Planned major surgery;
• Known aortic dissection;
• Have received any other clinical trial treatment within 1 year;
• Systemic treatment with corticosteroids or other systemic immunomodulatory therapy;
• Severe infections, including but not limited to infections requiring hospitalization, bacteremia, severe pneumonia, etc.;
• Known or suspected inherited connective tissue disorder;
• Calculated creatinine clearance of less than 30 ml/min;
• Known significant liver disease;
• Known human immunodeficiency virus infection at the time of screening；
• Serious concomitant illness associated with life expectancy of less than 2 years；
• Any other significant and unstable condition that could limit compliance with the trial protocol.