Mediterranean Diet, Circuit Resistance Training, Empagliflozin in Elderly With Type 2 Diabetes: a Study Protocol

NCT03560375 | Completed Phase 4

• 1 other identifier: TLV-0816-17
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Primary objective: To assess the effects of a modified plant-based Mediterranean diet (vegeterranean diet), circuit resistance training (CRT) and empagliflozin alone or in combination on metabolic and physical function in elderly subjects with type 2 diabetes. The rationale for this study is to assess three interventions associated with a negative energy/caloric balance (increased caloric use in exercise, caloric restriction in the vegeterranean diet and caloric wasting by glycosuria with empagliflozin), their interaction and effect on body composition and physical function. Methods and analysis: One hundred men and women ≥ 65 years of age with type 2 diabetes, and low levels of physical activity will be randomized (1:1:1 manner, gender-stratified) for 10 weeks to one of 3 parallel arms: CRT consisting of 3 home sessions/week; ad-libitum plant-based Mediterranean diet (limited consumption of eggs, dairy and fish, avoidance of red meat and poultry) or empagliflozin 10mg/day. After 10 weeks CRT will be added to the empagliflozin or diet arms for an additional 10 weeks. Allocation concealment and blinding of primary outcome assessors will be implemented. Efficacy will be determined by assessment of lean body mass, body weight, fat mass %, sarcopenia measures (such as strength and physical function), HbA1c and blood pressure as well as other outcomes (both objective and subjective). Safety will be evaluated by routine monitoring of adverse events. This study was approved by the Tel-Aviv Sourasky Medical Center Institutional Review Board

Conditions

Diabetes Mellitus, Type 2; Sarcopenia; Weight Loss

Keywords

Type 2 diabetes; Sarcopenia; Weight loss; Physical function; Metabolic control; Older adults

Outcome Measures

Primary Outcomes (1)

• A composite of metabolic and functional indices

  In the 'metabolic index' 1 point was given for achieving a reduction of at least 2% in body fat, 2cm of waist circumference, 0.5% HbA1c and 5mmHg systolic blood pressure (final score 0-4). Metabolic threshold values that reflect the desired reduction were chosen based preferably on meta-analyses of randomized trials (or single RCT) that examined the impact of weight loss/lifestyle interventions (diet and/or physical exercise - focus on interventions as similar to our interventions) and pharmacotherapy (e.g., empagliflozin) in populations of overweight and obese (with/without diabetes) adults/ older adults. We reviewed the threshold values and set the final values taking into account the data reviewed for each metabolic variable.The 'functional index' awarded one point for preservation or increase in total skeletal muscle mass, HGS, isometric knee extension, and TUG results (final score 0-4).

  After 10 weeks (for all 3 arms) and after 20 weeks (for diet and drug arms only)

Secondary Outcomes (4)

• Change in fasting plasma glucose

  After 10 weeks (for all 3 arms) and after 20 weeks (for diet and drug arms only)

• Change in sarcopenia

  After 10 weeks (for all 3 arms) and after 20 weeks (for diet and drug arms only)

• Change in strength

  After 10 weeks (for all 3 arms) and after 20 weeks (for diet and drug arms only)

• Relative lean mass change

  after 10 weeks (for all 3 arms) and after 20 weeks (for diet and drug arms only)

Study Arms (3)

Circuit resistance training (CRT)

EXPERIMENTAL

2-3 circuits \* 10 exercises \* 3 times per week

Behavioral: Circuit resistance training (CRT)

Empagliflozin 10 MG

EXPERIMENTAL

10 mg once daily

Drug: Empagliflozin 10 MG

Vegeterranean diet (V-Med diet)

EXPERIMENTAL

The modified V-Med diet will be considered as ad-libitum (using fat sources), aimed for sufficient protein from animal and mainly plant-based sources with carbohydrates limitation.

Behavioral: Vegeterranean diet (V-Med diet)

Interventions

Circuit resistance training (CRT) BEHAVIORAL

Subjects will be allocated to CRT which consists of 10 resistance exercises for different body parts (=1 circuit) repeated 12-15 times, using modest weights (approximately 40-60% of one repetition maximum, RM). Each exercise is expected to be completed within 30-40 sec. The participant will move quickly (within 15-30 seconds) from one exercise to the next. The circuit will be repeated up to three times depending on the week of intervention. Thus, it will take about 30 min to complete an exercise session. For a summary of articles on CRT in older adults based on a meta-analysis, we performed please see: Circuit resistance training is an effective means to enhance muscle strength in older and middle-aged adults: A systematic review and meta-analysis. Ageing Res Rev. 2017 Aug;37:16-27

Circuit resistance training (CRT)

Vegeterranean diet (V-Med diet) BEHAVIORAL

The modified V-Med diet will be considered as ad-libitum (using fat sources) aimed for a minimum of 1 gr/kg/day of protein, limiting carbohydrates: 3 servings for men and 2 servings for women per main meal and 1 serving per intermediate meal for both genders. Subjects will be asked to avoid red meat and poultry completely and the consumption of dairy and eggs products will be limited to 2 servings per day. 2-3 servings of fish should be consumed during the week. The rest of protein consumption will be recommended from legumes sources. The target legume consumption will be 1.5 cup per day (2 servings per day) of cooked beans, chickpeas, lentils and/or using pulses-based flour or pulses-based bread. Consumption of whole grain carbohydrate foods will be recommended.

Vegeterranean diet (V-Med diet)

Empagliflozin 10 MG DRUG

Subjects allocated to empagliflozin will be asked to add empagliflozin 10mg, preferably in the morning, to their medication regimen. Subjects will be monitored for adverse events including hypoglycemic events during all study visits.

Empagliflozin 10 MG

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• Subjects who have type 2 diabetes mellitus in accordance with American Diabetes Association guidelines and:
• Are ≥65 years of age (inclusive) on the day of signing the informed consent form.
• Perform \<2 days a week of any leisure aerobic physical activity (PA), who are able to walk independently either with or without an assistance device (cane or walker).
• HbA1C ≥6.5% to ≤8%.

You may not qualify if:

• Recent use of steroid agents (\<6 months, replacement therapy is allowed)
• Uncorrected hypothyroidism \[thyroid stimulating hormone (TSH) \> 6 mlU/L\]
• Diagnosis of malignancy within the past 5 years except for non-melanoma skin cancer.
• Severe kidney disease (eGFR\<45cc/ml)
• Active depression
• Recent (≤6 months) or unstable cardiovascular condition; New York Heart Association (NYHA) Class 3 or higher congestive heart failure;
• Subjects with PA limiting pain due to neuropathy
• Subjects who are in an active nutritional therapy changed their diet recently (\<1 month) and/or in a weight-loss program (actively losing weight).
• Has other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or may interfere with the interpretation of study results.

Sponsors & Collaborators

• Tel-Aviv Sourasky Medical Center: lead

Study Sites (1)

The Institute of Endocrinology Metabolism and Hypertension

Tel Aviv, 64239, Israel

Location

Related Publications (2)

• Kis O, Buch A, Eldor R, Rubin A, Dunsky A, Stern N, Moran DS. Should knee extension strength testing be implemented as a screening test for identifying probable and confirmed sarcopenia in older T2DM patients? Eur Rev Aging Phys Act. 2022 Jan 27;19(1):5. doi: 10.1186/s11556-021-00280-y.

  PMID: 35086483 DERIVED

• Buch A, Eldor R, Kis O, Keinan-Boker L, Dunsky A, Rubin A, Lopez A, Sofer Y, Osher E, Marcus Y, Stern N. The effect of circuit resistance training, empagliflozin or "vegeterranean diet" on physical and metabolic function in older subjects with type 2 diabetes: a study protocol for a randomized control trial (CEV-65 trial). BMC Geriatr. 2019 Aug 22;19(1):228. doi: 10.1186/s12877-019-1219-7.

  PMID: 31438863 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2; Sarcopenia; Weight Loss

Interventions

empagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Body Weight Changes; Body Weight

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Allocation concealment and blinding of primary outcome assessors will be implemented
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: This is a single center, open-label (primary outcome assessors blinded), parallel group, clinical trial of circuit resistance training for 10 weeks; V-Med diet for 10 weeks and then circuit resistance training on top of diet for 10 weeks; empagliflozin 10mg/day for 10 weeks and then circuit resistance training on top of drug therapy for 10 weeks in subjects with type 2 diabetes mellitus

Study Record Dates

• First Submitted: May 6, 2018
• First Posted: June 18, 2018
• Study Start: May 9, 2018
• Primary Completion: February 10, 2021
• Study Completion: February 10, 2021
• Last Updated: September 4, 2025

Record last verified: 2018-06

Locations

IL (1)