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

NCT ID: NCT03560375

Last Updated: 2025-09-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 100 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-05-09
• Study Completion Date: 2021-02-10

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Circuit resistance training (CRT)

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

Group Type: EXPERIMENTAL

Circuit resistance training (CRT)

Intervention Type: 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

Empagliflozin 10 MG

10 mg once daily

Group Type: EXPERIMENTAL

Empagliflozin 10 MG

Intervention Type: 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.

Vegeterranean diet (V-Med diet)

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.

Group Type: EXPERIMENTAL

Vegeterranean diet (V-Med diet)

Intervention Type: 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.

Interventions

Circuit resistance training (CRT)

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

Intervention Type: BEHAVIORAL

Vegeterranean diet (V-Med diet)

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.

Intervention Type: BEHAVIORAL

Empagliflozin 10 MG

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.

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Subjects who have type 2 diabetes mellitus in accordance with American Diabetes Association guidelines and:

1. Are ≥65 years of age (inclusive) on the day of signing the informed consent form.

2. 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).

3. HbA1C ≥6.5% to ≤8%.

Exclusion Criteria

1. Recent use of steroid agents (<6 months, replacement therapy is allowed)

2. Uncorrected hypothyroidism [thyroid stimulating hormone (TSH) > 6 mlU/L]

3. Diagnosis of malignancy within the past 5 years except for non-melanoma skin cancer.

4. Severe kidney disease (eGFR<45cc/ml)

5. Active depression

6. Recent (≤6 months) or unstable cardiovascular condition; New York Heart Association (NYHA) Class 3 or higher congestive heart failure;

7. Subjects with PA limiting pain due to neuropathy

8. Subjects who are in an active nutritional therapy changed their diet recently (<1 month) and/or in a weight-loss program (actively losing weight).

9. 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.

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Tel-Aviv Sourasky Medical Center

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

The Institute of Endocrinology Metabolism and Hypertension

Tel Aviv, , Israel

Countries

Israel

References

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.

Reference Type: DERIVED

PMID: 35086483 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31438863 (View on PubMed)

Other Identifiers

TLV-0816-17

Identifier Type: -

Identifier Source: org_study_id