Alpha-Ketoglutarate and Abdominal Aortic Aneurysm Progression and Rupture

The Intervention Effect Of Alpha-Ketoglutarate On Abdominal Aortic Aneurysm Progression and Rupture: A Prospective, Randomized Parallel Controlled Study Based On Large Cohorts

The objective of this project is to define whether nutritional supplement (oral administration with alpha-ketoglutarate) capable of filling-up the citric acid cycle (anaplerotic therapy) can improve outcomes in patients with an abdominal aortic aneurysm of 39-49 mm in diameter on ultrasound imaging. Alpha-ketoglutarate is commonly used as a nutritional supplement specially by athletes to increase muscle strength. They can be mixed with formula or other foods. Subjects will be followed for up to 5 years.

Study Overview

• Status: Recruiting
• Conditions: Patients With an Abdominal Aortic Aneurysm of 39-49 mm in Diameter
• Intervention / Treatment: Dietary supplement: alpha-ketoglutarate

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Shanghai, China
    • Recruiting
    • Cardiology, Ren Ji Hospital
    • Contact: Jun Pu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: alpha-ketoglutarate Group; Take alpha-ketoglutarate supplements, alpha-ketoglutarate 300mg/d mixed with food or drink, for 1 years	Dietary supplement: alpha-ketoglutarate; alpha-ketoglutarate supplements
No Intervention: Normal Control Group; Don't take alpha-ketoglutarate supplements

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in aortic diameter	Measure the aortic diameter by ultrasound imaging from leading edge adventitia at the anterior wall to leading edge adventitia at the posterior wall.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rates of AAA repair/rupture	Calculate the incidence of AAA repair/rupture	1 year
Rates of mortality	Calculate the mortality due to AAA rupture	1 year
Changes level of plasma biomarker	Measure plasma levels of tryptase	1 year

Collaborators and Investigators

• Sponsor: RenJi Hospital
• Investigators: Principal Investigator: Jun Pu, Renji Hospital

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Anticipated): February 1, 2026
• Study Completion (Anticipated): December 31, 2026

Study Registration Dates

• First Submitted: January 21, 2021
• First Submitted That Met QC Criteria: January 22, 2021
• First Posted (Actual): January 26, 2021

Study Record Updates

• Last Update Posted (Actual): February 21, 2021
• Last Update Submitted That Met QC Criteria: February 18, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: cohort study
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Wounds and Injuries; Aortic Diseases; Rupture; Aneurysm; Aortic Aneurysm; Aortic Aneurysm, Abdominal
• Other Study ID Numbers: AKG Intervention study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No