Time Course Adaptations Using Deuterated Creatine (D3Cr) Method

Sarcopenia Clinical Trial

Official title:

Time Course Adaptations Using Deuterated Creatine (D3Cr) Method: A Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03573583
• Other study ID #: IRB201801249 - N
• Secondary ID: P30AG028740
• Status: Completed
• Phase: N/A
• Start date: February 1, 2019
• Est. completion date: August 1, 2020

Study information

• Verified date: September 2023
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 21
• Est. completion date: August 1, 2020
• Est. primary completion date: August 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Sarcopenia

Intervention

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.
• 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.

Locations

Country	Name	City	State
United States	UF Health at the University of Florida	Gainesville	Florida
United States	UF Institute on Aging Clinical and Translational Research Building	Gainesville	Florida

Sponsors (2)

Lead Sponsor	Collaborator
University of Florida	National Institute on Aging (NIA)

Country where clinical trial is conducted

United States, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	D3Cr Muscle Mass	Change in Muscle mass measured using D3Cr	Measured at baseline, week 8, and week 15
Secondary	Muscle mass by dual-energy x-ray absorptiometry (DEXA)	Change in Muscle mass measured by DEXA	Measured at baseline, week 8, and week 15
Secondary	Changes in the Short Physical Performance Battery (SPPB) between the groups	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).	Baseline, Week 8, and Week 15
Secondary	Changes to the 400m walk speed between the groups	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)	Baseline, Week 8, and Week 15
Secondary	Changes in the isometric hand grip strength between the groups	Grip strength is frequently used as a measure of upper body skeletal muscle function. Grip strength will be measured using the Jammar dynamometer	Baseline, Week 8, and Week 15
Secondary	Changes in the strength of the knee extensors between the groups	Leg strength will be assessed using Isokinetic dynamometry.	Baseline, Week 8, and Week 15
Secondary	Changes in power of the knee extensors between the groups	Leg strength will be assessed using Isokinetic dynamometry.	Baseline, Week 8, and Week 15
Secondary	Changes in PROMIS Physical function test	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	Baseline, Week 8, and Week 15