Metabolic and Functional Consequences of Aging in Health and Disease

Considerable heterogeneity in the aging population has been observed. The exceptional longevity of individuals reaching 100 years old, so-called centenarians may be an example of life-long healthy aging, or added years may be spent in poor health with decreased physical and cognitive functioning. Current knowledge of the aging experience and the trajectories of physical and cognitive decline across various age groups are not well-understood, yet crucial to prevent spending added years in disease. Hence, the study objective is to develop the metabolic profile associated with aging-related disorders measured as the incidence of impaired functional capacity, cognitive function, and/or well-being.

Study Overview

• Status: Not yet recruiting
• Conditions: Aging
• Intervention / Treatment: Other: Stable tracer infusion in a postabsorptive state

Detailed Description

Our lab developed a pulse method combining multiple stable tracers to study multiple metabolic pathways in the same individual simultaneously. By measuring whole-body metabolism in a large group of older adults, we may be able to unravel age-related deterioration in protein turnover (synthesis and breakdown) that contributes to impaired functional capacity. Metabolic profiles could explain differences in pathways in the aging process with a special interest in the metabolism of amino acids as they have been associated with aging-related disorders. Studies on the effect of aging on metabolism might serve as potential therapeutic targets.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Laura Ruebush, PhD; Phone Number: 979-422-1789; Email: le.ruebush@ctral.org
• Study Contact Backup: Name: Marielle Engelen, PhD; Phone Number: 979-422-1789; Email: mpkj.engelen@ctral.org

Study Locations

• United States
  • Texas
    • College Station, Texas, United States, 77845
      • Human Clinical Research Building
      • Contact: Laura Ruebush, PhD; Email: le.ruebush@ctral.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

We will screen 200 subjects (to complete n=100). This number includes screen failures and drop-outs. We expect some dropout between screening and enrollment. Subjects who drop out prior to the successful completion of the study will be replaced. Data will be used up to the point of withdrawal. Age range: 50 years or older, inclusive; Ethnicity: all races and ethnicities.

Description

Inclusion Criteria:

• Stable body-weight (± 5%) for the past 3 months
• Subject is judged to be in satisfactory health based on medical history, physical examination, and laboratory screening evaluations.
• Ability to walk, sit down and stand up independently or with walking mobility aids
• Ability to lie in a supine or elevated position for up to 3 hours
• Willingness and ability to comply with the protocol

Exclusion Criteria:

• Insulin dependent diabetes mellitus
• Established diagnosis of malignancy
• History of untreated metabolic diseases including hepatic or renal disorder
• Presence of acute illness or metabolically unstable chronic illness
• Presence of fever within the last 3 days
• Use of short course of oral corticosteroids within 4 weeks preceding study day
• Failure to give informed consent or Investigator's uncertainty about the willingness or ability of the subject to comply with the protocol requirements
• (Possible) pregnancy
• Already enrolled in another clinical trial and that clinical trial interferes with participating in this study

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Controls; Study subjects that are eligible based on inclusion/exclusion criteria Screening visit: body weight and composition by DXA, height, and vital signs will be assessed. Study day(s): may include combinations of stable tracer infusions and with blood draws, cognitive and muscle performance testing	Other: Stable tracer infusion in a postabsorptive state; Multiple stable-labeled tracers of amino acids, ketoacids, glycerol, short-chain fatty acids; Other Names: Stable tracer infusion

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age-related changes in whole-body protein and amino acid metabolism	Whole-body production rate measured after stable tracer administration	2 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age-related changes in whole-body glucose metabolism	Whole-body production rate measured after stable tracer administration	2 hours
Age-related changes in whole-body fat metabolism	Whole-body production rate measured after stable tracer administration	2 hours
Age-related changes in depression as measured by the Hospital Anxiety and Depression Scale (HADS) and Geriatric Depression Scale (if applicable)	Self-reported depression measured by a validated questionnaire related to depression. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms). A higher score indicates a worse outcome (greater self-reported depression symptoms).	baseline visit
Age-related changes in anxiety as measured by the Hospital Anxiety and Depression Scale (HADS)	Anxiety measured by a validated questionnaire related to anxiety-related symptoms. Each item on the questionnaire is scored from 0-3 and this means that a person can score between 0 (no symptoms) and 21 (severe symptoms) related to anxiety. A higher score indicates a worse outcome (greater self-reported anxiety symptoms).	baseline visit
Age-related changes in mood as measured by the Profile of Mood State (POMS)	A psychological distress scale to measure the mood disturbance in 6 domains - fatigue-inertia, vigor-activity, tension-anxiety, depression-dejection, anger-hostility, and confusion-bewilderment in the past week. Each item on the questionnaire is awarded a score from 0 ("not at all") to 4 ("extremely"), except "Relaxed" and "Efficient" scored 4 ("not at all") and 0 ("extremely"), based on the intensity of the assessed feeling in the past week.	baseline visit
Age-related changes in health status	Health status assessed by Health-Related Quality of Life Scale (HR-QoL)	baseline visit
Age-related changes in physical activity	Physical activity assessed by Physical Activity Scale for the Elderly (PASE)	baseline visit
Age-related changes in sleep quality	Sleep quality assessed by Pittsburgh Sleep Quality Index	baseline visit
Age-related changes in nutritional status	Nutritional status assessed by Mini-Nutritional Assessment	baseline visit
Age-related changes in attention and executive functions as measured by Trail Making Test (TMT)	In Part A, the examinee is instructed to connect a set of 25 circles with numbers as quickly as possible while maintaining accuracy. In Part B, the examinee is instructed to connect a set of 25 circles, alternating between numbers and letters, as quickly as possible while maintaining accuracy. Measures attentional resources and is a measure of the frontal lobe "executive" functions of visual search, set-switching and mental flexibility. The total time in seconds was reported for each measure.	baseline visit
Age-related changes in overall cognitive abilities as measured by Montreal Cognitive Assessment (MoCA)	MoCa assesses several cognitive domains and is used for the screening of mild cognitive impairment. Total scores range from 0-30 with lower scores indicating decreased functioning.	baseline visit
Age-related changes in exercise capacity	Functional exercise capacity assessed by 6-minute walk test	baseline visit
Age-related changes in physical weakness (frailty)	Physical weakness assessed by Short Physical Performance Battery	baseline visit
Age-related changes in skeletal muscle strength of the upper extremity	Skeletal muscle strength measured by handgrip test	baseline visit
Age-related changes in skeletal muscle strength of the lower extremity	Skeletal muscle strength measured by one-leg test	baseline visit
Age-related changes in respiratory muscle strength	Respiratory muscle strength measured by a hand-held mouth pressure device (Micro RPM)	baseline visit
Age-related changes in balance	Skeletal muscle strength measured by Berg Balance Scale and balance platform	baseline visit
Age-related changes in gut microbiota	The amount and types of microbiota assessed in collected stool sample	baseline visit
Age-related changes in gut function	Gut function assessed by Gastrointestinal Symptom Rating Scale, a 15-item instrument designed to assess the symptoms associated with common gastrointestinal disorders. A higher score indicates worse outcomes (more discomfort).	baseline visit

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Age-related changes in hand dexterity	Hand dexterity assessed by the Nine-Hole Peg Test (9-HPT), a standardized, quantitative assessment in which the subject is asked to take pegs from a container, one by one, and place them into the holes on the board. Time upon completion will be recorded using both left and right hand, separately.	baseline visit

Collaborators and Investigators

• Sponsor: Texas A&M University

Study record dates

Study Major Dates

• Study Start (Anticipated): March 1, 2022
• Primary Completion (Anticipated): February 1, 2025
• Study Completion (Anticipated): December 1, 2025

Study Registration Dates

• First Submitted: January 19, 2022
• First Submitted That Met QC Criteria: February 14, 2022
• First Posted (Actual): February 15, 2022

Study Record Updates

• Last Update Posted (Actual): February 15, 2022
• Last Update Submitted That Met QC Criteria: February 14, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: metabolism; disease; stable isotopes
• Other Study ID Numbers: 2021-1413; 82-Aging (Other Identifier: CTRAL)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Data may be shared upon request for up to 6 years beyond completion of the trial based on methods/proposal approved by both parties' institutional review committees. Individual participant data that underlie the results of the trial may be shared after de-identification (text, tables, figures, and appendices). Additional documents available per request include: study protocol, statistical analysis plan, and informed consent. Requests should be directed to Dr. Marielle Engelen (mpkj.engelen@ctral.org).

Drug and device information, study documents

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