Time Course Adaptations Using Deuterated Creatine (D3Cr) Method

Muscle loss with age is considered to be an important cause of disability in older adults.
However, current tools frequently used and recommended to measure muscle mass in trials have
limitations: For example, DEXA (Dual-energy X-ray absorptiometry) and BIA (Bioelectrical
impedance analysis)- both widely used in clinical trials cannot distinguish muscle tissue
from non-muscle elements such as subcutaneous and intramuscular fat, skin, water and
connective tissue.

Deuterated creatine (D3Cr) dilution is a novel promising method that provides an accurate
measure of the functional contractile tissue, without including the non-contractile elements,
by measuring total body creatine. Our preliminary cross-sectional results in men aged >65
years show functional muscle mass (FMM) assessed by D3-Cr to be significantly associated with
performance outcomes and long-term outcomes, while DEXA showed no associations. However,
these are observational data and cannot determine a causative role of muscle per se on
functional outcomes.

Hence, the objective of the pilot study is to assess the feasibility of our proposed future
study to evaluate the role of muscle mass on functional outcomes. Specifically, the pilot
study will randomize moderate to low-functioning older adults to a resistance training
program or successful aging health education program to assess recruitment yields,
participant adherence, retention, training program design aspects, sample size, and the cost
of the main trial. Further, the impact of these changes in FMM on short-term performance
outcomes, such as strength, walking speed, SPPB, self-reported measures, and balance will be
examined.

Inclusion Criteria:

- men and women aged 70 or greater

- at high risk for mobility disability based on lower extremity functional limitations
measured by Short Physical Performance battery (SPPB) with a score ≤ 8 out of 12

- could safely participate in the resistance training intervention as determined by
medical history and physical examination.

- willing to give informed consent to be randomized to either the resistance training
group or successful aging heath education comparison group and willing to follow the
study protocol

Exclusion Criteria:

- Severe cardiac disease, including NYHA Class III or IV congestive heart failure,
clinically significant aortic stenosis, history of cardiac arrest, use of a cardiac
defibrillator, or uncontrolled angina

- Myocardial infarction, major heart surgery, stroke, deep vein thrombosis, or pulmonary
embolus in the past 6 months

- Lung disease requiring either oral or injected steroids, or the use of supplemental
oxygen

- Short, portable mental status questionnaire with 3 or more errors

- Severe arthritis (either osteoarthritis or rheumatoid arthritis) that severely limits
mobility

- Severe lower back or shoulder pain that can worsen with weight lifting exercises.

- Cancer requiring treatment in the past 1 year (Melanomas excluded)

- Any present or recent history of severe psychiatric illness including depression that
might preclude providing informed consent, safe participation, or compliance
(self‐report and investigator judgement

- Development of chest pain or severe shortness of breath on the 400 m self-paced walk
test

- Parkinson's disease or other serious neurological disorders; renal disease requiring
dialysis; other illness of such severity that life expectancy is considered to be less
than 12 months

- Current diagnosis of schizophrenia, other psychotic disorders, or bipolar disorder

- Current consumption of more than 14 alcoholic drinks per week

- Uncontrolled hypertension (systolic blood pressure > 200 mm Hg and/or diastolic blood
pressure >110 mm Hg)

- Currently on testosterone, Dehydroepiandrosterone (DHEA), or anabolic steroids.

- Undergoing physical therapy involving the lower extremities

- Currently enrolled in another randomized trial involving a pharmaceutical or lifestyle
intervention. Observational studies are permitted

- Participation in progressive resistance exercise regimen ( ≥1 day/week) within the
previous 6 months prior to screening.

- Weight change (intentional or not) over the last 6 months of > 5% of body or plan to
lose or gain weight during the study

- Any other cardiovascular, pulmonary, orthopedic, neurologic, or other conditions that
in the opinion of the local clinician would preclude participation and successful
completion of the protocol

Temporary Exclusion Criteria:

- Recent bacterial/viral infection (e.g. pneumonia) (< 2 weeks);

- Acute febrile illness in past 2 months;

- Severe hypertension, e.g., SBP > 200 mm Hg, DBP > 110 mm Hg

- Major surgery or fracture or hip/knee replacement (< 6 months);

- Hospitalization within the last 6 months ( Not ER visits)