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VLCD & Adjuvant Exercise Effect in Overweight Diabetic Men (VLCDeXDM)

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ClinicalTrials.gov Identifier: NCT04957589
Recruitment Status : Recruiting
First Posted : July 12, 2021
Last Update Posted : July 12, 2021
Sponsor:
Information provided by (Responsible Party):
University of Nottingham

Brief Summary:
Sarcopenia is defined as the incremental age-related loss of skeletal muscle in humans which generally begins from forty years old. It is associated with an overall reduction in quality of life and increased morbidity and mortality. Patients with type two diabetes mellitus (T2DM) are particularly at risk of developing sarcopenia, partly due to the condition and also due to the common incidence after or during middle age. A promising recently-investigated and effective conservative approach to T2DM is through very low calorie diets (VLCD). Some studies have shown that the diabetic status of some patients can be reversed through VLCD. However, VLCD will theoretically result in an acceleration of sarcopenia. This presents as a limiting factor for the implementation of VLCD in this at-risk patient group. Skeletal muscle tissue is encouraged to grow in size or be maintained through two means - an increase in circulating protein breakdown products, or through resistance exercise (RE). Additionally, RE has been shown to increase the body's sensitivity to insulin, the main hormone which controls circulating glucose levels and is frequently impaired in T2DM, as well as temporarily decreasing glucose levels. The precise mechanism by which these happen is not fully understood yet. In this study, the effect of one form of RE (high intensity interval training, HIT) is used, with or without protein supplementation, in a VLCD in overweight, middle-aged male patients with T2DM. 12 patients are to be recruited into each group (interval training, resistance training, control) at our centre. Patient weight, markers of muscle protein synthesis, glucose levels and changes to blood vessels will be investigated before, during and after across a six week timeframe. Investigations will include muscle and fat biopsies, blood samples, ultrasound scans, strength testing, echocardiogram and deuterium oxide (D2O) isotope ingestion for later non-invasive body fluid sample mass spectrometric analysis.

Condition or disease Intervention/treatment Phase
Diabetes Mellitus Type 2 in Obese Dietary Supplement: Very Low Calorie Diet Dietary Supplement: Protein supplementation Other: High Intensity Interval Training Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a proof-of-concept, single centre, randomised, non-blinded control trial.
Masking: None (Open Label)
Masking Description: Masking is infeasible, as the participants will know which intervention they are partaking in.
Primary Purpose: Treatment
Official Title: The Effect of a Very Low Calorie Diet (VLCD) With and Without Concomitant High Intensity Interval Training (HIIT) Paired With Protein Supplementation on Muscle Protein Synthesis (MPS) in Middle-aged Overweight Diabetic Men
Actual Study Start Date : January 1, 2020
Estimated Primary Completion Date : December 1, 2022
Estimated Study Completion Date : December 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: VLCD & HIIT & protein supplementation
Very low calorie diet (standardised LighterLife meal replacement packages consisting of approximately 150kcal each, amounting to 600kcal/day, no free expenditure) High intensity interval training (3x sessions per week following intensity estimation using cardiorespiratory testing (VO2max), using an established training protocol within our department) 200kcal/day whey protein supplementation
Dietary Supplement: Very Low Calorie Diet
A dietary intervention consisting of four meals (provided by LighterLife®), totaling approximately 600kcal/day (each meal comprising approximately 150kcal/day). Participants are provided with a choice of one of six "meal protocols", which consist of a pre-set combination of meals that arrive at approximately 52g protein, more than 15g fibre and less than 20g sugar per day.
Other Names:
  • LighterLife®
  • Very Low Energy Diet
  • Calorie Restriction
  • Caloric Restriction

Dietary Supplement: Protein supplementation
200kcal/day whey protein (approximately 38g protein), provided to the intervention arm.
Other Name: Whey protein (MYPROTEIN™)

Experimental: VLCD & HIIT
Very low calorie diet (standardised LighterLife meal replacement packages consisting of approximately 150kcal each, amounting to 600kcal/day, with 200kcal of a pre-determined free expenditure consisting of nuts and/or vegetables) High intensity interval training (3x sessions per week following intensity estimation using cardiorespiratory testing (VO2max), using an established training protocol within our department) No additional protein supplementation
Dietary Supplement: Very Low Calorie Diet
A dietary intervention consisting of four meals (provided by LighterLife®), totaling approximately 600kcal/day (each meal comprising approximately 150kcal/day). Participants are provided with a choice of one of six "meal protocols", which consist of a pre-set combination of meals that arrive at approximately 52g protein, more than 15g fibre and less than 20g sugar per day.
Other Names:
  • LighterLife®
  • Very Low Energy Diet
  • Calorie Restriction
  • Caloric Restriction

Dietary Supplement: Protein supplementation
200kcal/day whey protein (approximately 38g protein), provided to the intervention arm.
Other Name: Whey protein (MYPROTEIN™)

Other: High Intensity Interval Training
The HIIT training will consist of a five-exercise approach across three movements (star jumps, standing squats, on-the-spot-sprinting, standing squats and star jumps), which are collectively described as a cycle in this context. Each exercise is performed for 60 seconds with a 90 seconds recovery period. Each training session will begin with a two minute warm-up and cooldown (on-the-spot-jogging) followed by five minutes of static stretching. Volunteers would aim to exceed the initial number of star jumps and standing squats in the subsequent attempt per cycle. A total of three training sessions per week are to be completed, preferably non-consecutive but may be consecutive on no more than two training sessions per week. Progression is through a gradual increase in volume (repetitions of star jumps and standing squats) on a per-session basis.
Other Names:
  • HIIT
  • Home HIIT

Active Comparator: VLCD only
Very low calorie diet (standardised LighterLife meal replacement packages consisting of approximately 150kcal each, amounting to 600kcal/day, with 200kcal of a pre-determined free expenditure consisting of nuts and/or vegetables) No additional exercise or protein supplementation
Dietary Supplement: Very Low Calorie Diet
A dietary intervention consisting of four meals (provided by LighterLife®), totaling approximately 600kcal/day (each meal comprising approximately 150kcal/day). Participants are provided with a choice of one of six "meal protocols", which consist of a pre-set combination of meals that arrive at approximately 52g protein, more than 15g fibre and less than 20g sugar per day.
Other Names:
  • LighterLife®
  • Very Low Energy Diet
  • Calorie Restriction
  • Caloric Restriction




Primary Outcome Measures :
  1. Muscle Protein Synthesis (MPS) [ Time Frame: 6 weeks (throughout intervention) ]
    Estimation via weekly sampling of saliva following deuterium oxide (D2O) tracer solution administration relative to baseline.

  2. Muscle Protein Breakdown (MPB) (3MH) [ Time Frame: 6 weeks (one day prior to intervention study dates in pre, peri and post periods) ]
    Estimation via peri-intervention study date measurement of serum and urine 3-methylhistidine (3MH) concentration relative to baseline.


Secondary Outcome Measures :
  1. Vascular function (femoral artery blood flow) [ Time Frame: 6 weeks (pre and post intervention study dates only) ]
    Macrovascular assessment of femoral artery blood flow, assessed pre- and post- leg extension in the participant's dominant leg.

  2. Vascular function (contrast enhanced ultrasound scan) [ Time Frame: 6 weeks (pre and post intervention study dates only) ]
    Microvascular assessment of the vastus lateralis muscle in the participant's non-dominant leg using ultrasound scanning and Sonovue contrast agent.

  3. Vascular function (brachial artery reactive hyperaemia) [ Time Frame: 6 weeks (pre and post intervention study dates only) ]
    Microvascular assessment of the brachial artery's endothelial response to transient ischaemia through the application of a fixed cuff and an assessment of the wave-forms.

  4. Body composition (Dual-Energy X-ray Absorptiometry (DEXA) scan) [ Time Frame: 6 weeks (pre and post intervention study dates only) ]
    Assessment of participant body composition, including total mass, fat mass, lean body mass, and adipose tissue deposition pattern changes.

  5. Body composition (body weight measurement) [ Time Frame: 6 weeks (pre and post intervention study dates only) ]
    Measurement of participant weight (in kg).

  6. Body composition (body mass index (BMI) estimation) [ Time Frame: 6 weeks (pre and post intervention study dates only) ]
    Calculation of participant BMI using Outcome 7 and the participant's height from screening.

  7. Muscle structure (vastus lateralis cross-sectional area) [ Time Frame: 6 weeks (pre and post intervention study dates only) ]
    Measured through external ultrasound scanning.

  8. Muscle structure (vastus lateralis pennation angle) [ Time Frame: 6 weeks (pre and post intervention study dates only) ]
    Measured through external ultrasound scanning.

  9. Muscle structure (vastus lateralis circumference) [ Time Frame: 6 weeks (pre and post intervention study dates only) ]
    Measured through external ultrasound scanning.

  10. Muscle structure (vastus lateralis fascicle length) [ Time Frame: 6 weeks (pre and post intervention study dates only) ]
    Measured through external ultrasound scanning.

  11. Muscle function (1-repetition maximum assessment) [ Time Frame: 6 weeks (pre and post intervention study dates only) ]
    1-repetition maximum strength assessment in the bench press, cable row, lat pulldown, leg press, leg curl, leg extension: performed through several supervised warming-up exercise sets each, followed by a single maximum effort set, with the 1-repetition maximum calculated thereafter.

  12. Muscle function (maximum voluntary contraction) [ Time Frame: 6 weeks (pre and post intervention study dates only) ]
    Assessment of voluntary contraction of the quadriceps muscle.

  13. Metabolic status (Oral glucose tolerance testing (OGTT)) [ Time Frame: 6 weeks (pre and post intervention study dates only) ]
    Undertaken to assess for insulin sensitivity and resistance.

  14. Metabolic status (screening blood testing via venepuncture) [ Time Frame: 6 weeks (pre and post intervention study dates only) ]
    Repeat of screening blood battery testing (full blood count, urea and electrolytes, liver function test, thyroid function test, lipid profile). In each instance, the results are compared against the local laboratory reference range for the respective physiological parameters.

  15. Metabolic status (mitochondrial respiration) [ Time Frame: 6 weeks (pre and post intervention study dates only) ]
    Assessed via sampling of muscle tissue (vastus lateralis) via biopsy. Sample processed using Oroboros Instruments O2k machine. Oxygen consumption rate calculated.

  16. Cardiopulmonary fitness [ Time Frame: 6 weeks (pre and post intervention study dates only) ]
    Ergometer-based assessment of VO2max

  17. Skeletal Muscle & Creatine Pool Assessment (D3-C) [ Time Frame: 6 weeks (pre and post intervention study dates only) ]
    Total-body creatine pool size and skeletal muscle mass determination using D3-Creatine (D3-C).



Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must be able to provide informed consent.
  • Adult patients between the age of 30-65 years
  • A body mass index (BMI) of between 27-50
  • Confirmed Type 2 Diabetes Mellitus (T2DM)

Exclusion Criteria:

  • contrast (Sonovue) sensitivity,
  • known renal, musculoskeletal, neurological, bowel, cardiovascular, respiratory or cerebrovascular disease,
  • or current/recent formal exercise regime participation (within two years).
  • Prospective volunteers with a weight exceeding 120kg are ineligible to participate due to the weight restriction present in the DEXA machine.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04957589


Contacts
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Contact: Iskandar Idris, BMBS FRCP DM 01332724605 iskandar.idris@nottingham.ac.uk

Locations
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United Kingdom
Royal Derby Hospital Recruiting
Derby, Derbyshire, United Kingdom, DE22 3NE
Contact: Teresa Grieve, PhD    01332 724710    dhft.sponsor@nhs.net   
Sponsors and Collaborators
University of Nottingham
Investigators
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Principal Investigator: Iskandar Idris, BMBS FRCP DM University of Nottingham
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Responsible Party: University of Nottingham
ClinicalTrials.gov Identifier: NCT04957589    
Other Study ID Numbers: 19026_CMMP
255016 ( Other Identifier: IRAS )
First Posted: July 12, 2021    Key Record Dates
Last Update Posted: July 12, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description:

Individual participant medical information obtained as a result of this study are considered confidential and disclosure to third parties is prohibited with the exceptions noted above.

Such medical information may be given to the participant's medical team and all appropriate medical personnel responsible for the participant's welfare.

If information is disclosed during the study that could pose a risk of harm to the participant or others, the researcher will discuss this with the Chief Investigator (CI) and where appropriate report accordingly.

Data generated as a result of this trial will be available for inspection on request by the participating physicians, the University of Nottingham representatives, the local Research Ethics Committee (REC) and the regulatory authorities.

Elements of the results from this study will be submitted for peer-review in at least one publication.


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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Diabetes Mellitus, Type 2
Overweight
Body Weight
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases