Clinical trial NCT03573583: Time Course Adaptations Using Deuterated Creatine (D3Cr) Method
Official title: Time Course Adaptations Using Deuterated Creatine (D3Cr) Method: A Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sarcopenia
Keywords: muscle mass
muscle loss
Deuterated creatine (D3Cr) dilution
older adults
resistance training
physical function
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2018-06-29
Enrollment: 21
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The pilot study will be single-blind, parallel group, randomized controlled trial of 24 moderate to low functioning participants randomized in a 1:1 allocation ratio to a high-intensity Resistance Training group (RT) or a Successful Aging Health Education comparator group (HE) for 14 weeks.
Primary purpose: BASIC_SCIENCE

Brief summary: The pilot study is to assess the feasibility of using a new method to measure muscle mass called Deuterated Creatine (D3Cr) method and thereby understand the role of muscle mass on functional outcomes in older adults.

Detailed description: 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.

Eligibility criteria: 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)

Primary outcomes:
measure: Muscle Mass
timeFrame: Baseline and week 16
Secondary outcomes:
measure: Appendicular Lean Mass (ALM)
timeFrame: Baseline and week 16
measure: Lean Body Mass (LBM)
timeFrame: Baseline, and Week 16
measure: Correlation Between Changes in Muscle Mass
timeFrame: Baseline and Week 15
Other outcomes:
Locations:
city: Gainesville
country: United States
facility: UF Health at the University of Florida
state: Florida
city: Gainesville
country: United States
facility: UF Institute on Aging Clinical and Translational Research Building
state: Florida
Study officials:
affiliation: University of Florida
name: Todd Manini, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Balachandran AT, Evans WJ, Cawthon PM, Wang Y, Shankaran M, Hellerstein MK, Qiu P, Manini T. Comparing D3-Creatine Dilution and Dual-Energy X-ray Absorptiometry Muscle Mass Responses to Strength Training in Low-Functioning Older Adults. J Gerontol A Biol Sci Med Sci. 2023 Aug 27;78(9):1591-1596. doi: 10.1093/gerona/glad047.