Determinants of Alpha-aminoadipic Acid (2-AAA) and Relationship to Diabetes: Study 2

This study aims to assess the effect of controlled dietary lysine intake on plasma and urine α-aminoadipic acid (2-AAA).

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Dietary supplement: Controlled Diet; Dietary supplement: Lysine

Detailed Description

Diabetes is an important health concern worldwide. It is associated with significantly increased mortality as well as high incidence of co-morbidities. Unfortunately, treatment efficacy and successful disease management is highly variable among treated patients, and this is partly due to the fact that diabetes has multiple underlying causes most of which are still unknown. A newly identified biomarker, α-aminoadipic acid (2-AAA), has the potential to successfully predict the development of diabetes in humans, even before the development of other known risk markers. However, little is known about the function of 2-AAA; it is unclear whether 2-AAA itself causes the development of diabetes or if it is a biomarker for altered metabolic processes that then lead to diabetes.

The aim of the first phase of the study was to measure plasma 2-AAA levels from healthy individuals from the general population to identify subjects with high or low 2-AAA. Now in the second phase of the study, 80 subjects with high or low 2-AAA will be invited to participate in a dietary lysine modification study to access the effect of controlled lysine intake on plasma and urine 2AAA. Participants will be asked to complete two one-week dietary interventions. Subjects will be screened and consented via email, online, or phone. Each subject will be required to come to Vanderbilt University Medical Center for four study visits, at which the study team will obtain a blood sample, a urine sample, stool sample, vital signs, waist and hip circumference, and 1-3 surveys will be completed if the subject did not complete them prior to the visit. Each subject that completes the entire study visit will be compensated $250. DNA samples will be obtained to allow for identification of genetic predictors of 2-AAA levels. Some individuals may be asked to return for a future follow-up study.

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37212
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Prior participant in 2-AAA screening study.
• Identified as eligible due to high or low plasma 2-AAA, in the absence of hyperglycemia, as defined by study team.

Exclusion Criteria:

• Individuals who currently use tobacco products.
• Use of prescription or over-the-counter medications or dietary supplements which could modulate levels of 2-AAA and unwilling to discontinue use (from 24 hours prior to first study visit until completion of study). Hormonal birth control is acceptable.
• Follow a severely restricted diet or have food allergies, which would preclude adherence to study diet.
• Newly diagnosed disease (since screening visit), including cardiovascular, renal, or liver disease, or Diabetes mellitus.
• Individuals who are pregnant or lactating
• Inability to provide written or electronic informed consent
• Inability to fast for 8 hours

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Normal Lysine Diet; Participants will complete two one-week dietary interventions, in a randomized order. For the normal lysine diet, participants will be asked to adhere to a specific diet for 1 week. Each study subject will receive 3 meals and 1-2 snacks per day during the study period.	Dietary supplement: Controlled Diet; Individuals will be instructed to consume specific foods, to adhere to a controlled lysine diet.
Experimental: High Lysine Diet; Participants will complete two one-week dietary interventions, in a randomized order. For the high lysine diet, participants will be asked to consume the same foods as in the normal lysine diet, but with the addition of lysine supplements (5g/day).	Dietary supplement: Controlled Diet; Individuals will be instructed to consume specific foods, to adhere to a controlled lysine diet.; Dietary supplement: Lysine; Lysine is an essential amino acid which is acquired from dietary sources.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Plasma 2-AAA Concentration From Baseline	Alpha aminoadipic acid (2-AAA) concentration determined through mass spectrometry, quantified to standard. The change was calculated as post-diet minus pre-diet for each Intervention (Normal lysine and High lysine).	Change from pre-diet to post-diet (1 week)

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Study record dates

Study Major Dates

• Study Start (Actual): August 17, 2020
• Primary Completion (Actual): January 1, 2023
• Study Completion (Actual): January 1, 2023

Study Registration Dates

• First Submitted: June 2, 2020
• First Submitted That Met QC Criteria: June 2, 2020
• First Posted (Actual): June 4, 2020

Study Record Updates

• Last Update Posted (Actual): December 21, 2023
• Last Update Submitted That Met QC Criteria: December 20, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: 200427; R01DK117144 (U.S. NIH Grant/Contract)

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
• product manufactured in and exported from the U.S.: No