Measuring Protein Turnover in Humans Across the Lifespan by Metabolic Labeling With Deuterium Oxide

NCT06269653 | Recruiting

• 2 other identifiers: 10001944001944-AG
• Study Type: observational
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Proteins are essential to the health and structure of the cells that make up body tissues. Most proteins become damaged over time and are replaced with new ones. This process is called "protein turnover." Stress, disease, and aging can affect this process. Researchers want to better understand how aging affects protein turnover. Objective: To measure rates of protein turnover in healthy adults. Eligibility: Healthy people aged 20 years and older with a body mass index between 20 and 30. Design: Participants will have 6 study visits over 4 to 6 weeks. They will fast 12 hours before each visit. Participants will be screened. They will have a physical exam, with blood and urine tests and tests of their heart function. They will lie down while blood pressure cuffs are used on their arms and legs. Participants will be given bottles of heavy water to drink at home on a schedule for 21 days. Each bottle holds about 3.5 tablespoons. Heavy water is odorless, colorless, and tasteless, like normal drinking water. It is safe to drink and has been used in research for many years. Participants will have tests during study visits, including: Imaging scans of a leg. Exercise on a treadmill. Biopsies of muscle, skin, and fat: Small samples of tissue will be cut from the calf and abdomen. Resting metabolic rate: Participants will lie still and breathe into a mask for 20 minutes. Knee/grip strength: Participants will do strength tests with their legs. They will squeeze a device with their hands. D3-Creatine: Participants will take 1 pill of D3-Creatine, which occurs naturally in muscle.

Conditions

Healthy Volunteers

Keywords

PROTEIN TURNOVER; Metabolic; Mononucleated Cells; Mitochondrial; Peripheral

Outcome Measures

Primary Outcomes (1)

• Measure the turnover proteins in humans across tissues, age, and sex.

  No data is available on proteins half-life that compare different tissues in humans; and this information would be important to interpret proteomic data. Comprehensively profile the turnover rates and half-lives of different proteins in human skeletal muscle.

  21 days

Secondary Outcomes (1)

• Test the hypothesis that older age is associated with diminished protein turnover.

  24 months

Study Arms (6)

Healthy Individuals: 20 - 29 years of age

Age group: 20 -29 (3 men and 3 women)

Healthy Individuals: 30 - 39 year of age

Age group: 30 - 39 (3 men and 3 women)

Healthy Individuals: 40 - 49 years of age

Age group 40 - 49 (3 men and 3 women)

Healthy Individuals: 50 - 59 years of age

Age group: 50 - 59 (3 men and 3 women)

Healthy Individuals: 60 - 69 years of age

Age group: 60 - 69 (3 men and 3 women)

Healthy Individuals: 70 +

Age group: 70+ (3 men and 3 women)

Eligibility Criteria

• Age: 20 Years - 120 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants will be enrolled into the following age-groups: 20-29; 30-39; 40-49; 50-59; 60-69; 70-plus years with 6 participants (3 men and 3 women) in each age group.

You may qualify if:

• To be eligible to participate in this study, an individual must meet all the following criteria:
• Stated willingness to comply with all study procedures and availability for the duration of the study.
• Male or female, age \>= 20years.
• BMI \>20 and \<30.
• In good general health as evidenced by medical history/exam/laboratory.
• IL6\< 3.5 pg/mL.
• Ankle Brachial Index (ABI) \> 0.9.
• No history of increased bleeding due to either a known medical condition or an undiagnosed cause.
• Does not currently smoke/tobacco use.
• Eligible for muscle biopsy procedures.
• Is not allergic to lidocaine or other local anesthetics.
• Able to speak and read English.
• Ability of subject to understand and the willingness to sign a written informed consent document.

You may not qualify if:

• An individual who meets any of the following criteria will be excluded from participation in this study:
• Routinely taking (more than 2x/week) non-steroidal anti-inflammatory agents (NSAIDs) and unwilling to stop taking them for the duration of the study.
• Taking medications that could increase the chance of bleeding such as anticoagulants/antiplatelet such as Coumadin, Plavix, and Heparin. Low dose (81mg) aspirin use is okay.
• Is unable to reach down to perform wound care of the lower legs.
• Has laboratory evidence of diabetes at screening (fasting glucose \>= 126) and/or diabetes requiring treatment, or treatment with any glucose lowering drug(s).
• Has current or history of inflammatory and/or autoimmune diseases.
• History of keloid formation.
• Researchers are unable to access biopsy sites due to conditions such as wounds, rashes, or large deposits of adipose tissue.
• Is on treatment with an investigational drug or other intervention within 8 weeks of enrollment.
• Has any chronic disease that the study PI considers as a significant comorbidity that affects health and life expectancy.
• Has established genetic diseases such as sickle cell, hemochromatosis (iron overload), cystic fibrosis or Ehlers-Danlos syndrome (connective tissue disorder).
• Has autoimmune diseases such as Hashimoto s thyroiditis, Myasthenia Gravis, or Rheumatoid arthritis.
• Has severe mobility disability as evidenced by inability to walk without aids, perform activities of daily living and to reach down to lower legs to perform wound care.
• Has had active cancer on treatment in the last 10 years.
• Has muscle-skeletal conditions due to diseases or traumas (that cause pathological weakness and/or chronic pain).

Sponsors & Collaborators

• National Institute on Aging (NIA): lead

Study Sites (1)

National Institute of Aging, Clinical Research Unit

Baltimore, Maryland, 21224, United States

RECRUITING

Study Officials

• Luigi Ferrucci, M.D.

  National Institute on Aging (NIA)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Linda M Zukley, Ph.D.

CONTACT

(410) 350-3983; zukleylm@mail.nih.gov

Luigi Ferrucci, M.D.

CONTACT

(410) 558-8110; ferruccilu@grc.nia.nih.gov

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 16, 2024
• First Posted: February 21, 2024
• Study Start: June 26, 2024
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: March 20, 2026

Record last verified: 2026-02-24

Locations

US (1)