Healthy
Conditions
Brief summary
This study aims to assess the effect of controlled dietary lysine intake on plasma and urine α-aminoadipic acid (2-AAA).
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.
Interventions
DIETARY_SUPPLEMENTLysine
Lysine is an essential amino acid which is acquired from dietary sources.
DIETARY_SUPPLEMENTControlled Diet
Individuals will be instructed to consume specific foods, to adhere to a controlled lysine diet.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Vanderbilt University Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Plasma 2-AAA Concentration From Baseline | Change from pre-diet to post-diet (1 week) | 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). |
Countries
United States
Participant flow
Pre-assignment details
N=20 enrolled individuals withdrew or were lost to follow up prior to starting the intervention.
Participants by arm
| Arm | Count |
|---|---|
| Dietary Intervention 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.
Controlled Diet: Individuals will be instructed to consume specific foods, to adhere to a controlled lysine diet.
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).
Lysine: Lysine is an essential amino acid which is acquired from dietary sources. | 47 |
| Total | 47 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| First Intervention (1 Week)) | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Dietary Intervention |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 47 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 7 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 34 Participants |
| Region of Enrollment United States | 47 participants |
| Sex: Female, Male Female | 30 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 47 | 0 / 46 |
| other Total, other adverse events | 2 / 47 | 7 / 46 |
| serious Total, serious adverse events | 0 / 47 | 0 / 46 |
Outcome results
Primary
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).
Time frame: Change from pre-diet to post-diet (1 week)
Population: Individuals were included for analysis only if they had provided a blood sample for measurement of 2-AAA at both the pre- and post-diet timepoints. This excluded 3 individuals from the normal lysine diet intervention, and 4 individuals from the high lysine diet intervention.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Normal Lysine Diet | Change in Plasma 2-AAA Concentration From Baseline | -9.35 ng/ml | Standard Deviation 30.3 |
| High Lysine Diet | Change in Plasma 2-AAA Concentration From Baseline | 7.02 ng/ml | Standard Deviation 23.7 |