Time Course Adaptations Using Deuterated Creatine (D3Cr) Method

• ClinicalTrials.gov Identifier: NCT03573583
• Recruitment Status: Active, not recruiting
• First Posted: June 29, 2018
• Last Update Posted: June 7, 2021
• Sponsor: University of Florida
• Collaborator: National Institute on Aging (NIA)
• Information provided by (Responsible Party): University of Florida

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Sarcopenia	Behavioral: Resistance Training; Behavioral: Successful Aging	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 21 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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.
• Masking: Single (Outcomes Assessor)

Masking Description

To ensure concealment of the allocation, the randomization procedures will be performed by an investigator who are not involved in the assessments.

The team assessing study outcomes will be masked to intervention assignment.

• Primary Purpose: Basic Science
• Official Title: Time Course Adaptations Using Deuterated Creatine (D3Cr) Method: A Pilot Study
• Actual Study Start Date: February 1, 2019
• Actual Primary Completion Date: August 1, 2020
• Estimated Study Completion Date: March 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Resistance Training group (RT); The resistance training intervention will include a full body, resistance training performed three days per week. The intensity, volume, tempo, and progression will be based on the Federal Physical Activity guidelines	Behavioral: Resistance Training; The intensity, volume, tempo, and progression will be based on the Federal Physical Activity guidelines. The resistance training exercises will include mainly multi-joint exercises using selectorized machines. Each session will include upper body exercises (Chest Press, Shoulder Press, Seated Rows, Bicep curls, and Tricep Extensions) and lower body exercises (Leg Press, Leg Extension and Leg Curls, and Calf raise) that will be tailored to the participant needs.; Other Names: RT; Strength Training; Weight Training
Active Comparator: Successful Aging; The comparator group will meet for stretching and health education classes every 2-5 weeks up to 7 total visits.	Behavioral: Successful Aging; The successful aging will attend stretching and health lectures as a group . The topics might include, medication management, disease management (e.g. blood pressure, diabetes, arthritis, dementia, pain management, diet) and other health related matters.; Other Names: HE; Health Education

Outcome Measures

Primary Outcome Measures :

1. D3Cr Muscle Mass [ Time Frame: Measured at baseline, week 8, and week 15 ]
   Change in Muscle mass measured using D3Cr

Secondary Outcome Measures :

1. Muscle mass by dual-energy x-ray absorptiometry (DEXA) [ Time Frame: Measured at baseline, week 8, and week 15 ]
   Change in Muscle mass measured by DEXA
2. Changes in the Short Physical Performance Battery (SPPB) between the groups [ Time Frame: Baseline, Week 8, and Week 15 ]
   Physical performance will be measured using the Short Physical Performance Battery (SPPB), which is based on a timed 4-m walk, balance, and chair stand tests. This scale is reliable and valid for predicting institutionalization, mortality and disability. The score ranges from 0 (worst performers) to 12 (best performers).
3. Changes to the 400m walk speed between the groups [ Time Frame: Baseline, Week 8, and Week 15 ]
   The 400m walk test is a feasible, objective, reliable, well-validated and used in large clinical trial. Participants will be asked to walk 400 m at their usual pace, without overexerting, on a 20-m course for 10 laps (40 m/lap)
4. Changes in the isometric hand grip strength between the groups [ Time Frame: Baseline, Week 8, and Week 15 ]
   Grip strength is frequently used as a measure of upper body skeletal muscle function. Grip strength will be measured using the Jammar dynamometer
5. Changes in the strength of the knee extensors between the groups [ Time Frame: Baseline, Week 8, and Week 15 ]
   Leg strength will be assessed using Isokinetic dynamometry.
6. Changes in power of the knee extensors between the groups [ Time Frame: Baseline, Week 8, and Week 15 ]
   Leg strength will be assessed using Isokinetic dynamometry.
7. Changes in PROMIS Physical function test [ Time Frame: Baseline, Week 8, and Week 15 ]
   The NIH developed Patient-Reported Outcomes Measurement Information System (PROMIS) physical function questionnaire uses item response theory (IRT) and computer adaptive tests (CAT) to improve precision and minimize respondent burden

Eligibility Criteria

• Ages Eligible for Study: 70 Years and older (Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)

Contacts and Locations

Locations

United States, Florida

UF Health at the University of Florida

Gainesville, Florida, United States, 32610

UF Institute on Aging Clinical and Translational Research Building

Gainesville, Florida, United States, 32611

Sponsors and Collaborators

University of Florida

National Institute on Aging (NIA)

Investigators

• Principal Investigator: Todd Manini, PhD; University of Florida

More Information

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT03573583
• Other Study ID Numbers: IRB201801249 - N; P30AG028740 ( U.S. NIH Grant/Contract )
• First Posted: June 29, 2018
• Last Update Posted: June 7, 2021
• Last Verified: June 2021

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Florida:

muscle mass; muscle loss; Deuterated creatine (D3Cr) dilution; older adults; resistance training; physical function

Additional relevant MeSH terms:

Sarcopenia; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical