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Diabetes Interventional Assessment of Slimming or Training to Lessen Inconspicuous Cardiovascular Dysfunction (Diastolic)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02590822
Recruitment Status : Active, not recruiting
First Posted : October 29, 2015
Last Update Posted : January 30, 2020
Sponsor:
Collaborators:
University Hospitals, Leicester
National Institute for Health Research, United Kingdom
Information provided by (Responsible Party):
University of Leicester

Brief Summary:

There is an epidemic of type 2 diabetes in younger adults. These patients are at very high lifetime risk of heart-related complications. Subtle heart abnormalities can be present even at a young age in these patients and may predispose them to heart failure and ultimately premature death. There is emerging evidence that type 2 diabetes can be reversed with weight loss. We propose that weight loss can also reverse the fatty changes seen in the liver and heart in these patients, and in turn lead to improved heart function.

This project aims to identify how type 2 diabetes causes changes in the heart in young people with type 2 diabetes by performing detailed scans and other tests of the heart's structure and function. In addition we will attempt to see if the heart's pumping function can be improved, either by a weight loss program with a special low calorie diet, or by a structured program of exercise. This will be compared with the usual standard diabetes care.

As well as looking to see if the heart's function can be improved with the intervention, we also aim to identify what the mechanism of any improvement would be. We suspect that changes in the amount of fat within the liver and the heart may be responsible, and will measure these at the beginning, end and in some patients halfway through the study to explore possible mechanisms amongst other clinical variables (e.g. HbA1c)


Condition or disease Intervention/treatment Phase
Diabetes Dietary Supplement: Cambridge Weight Plan Other: Supervised Exercise Sessions Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Diabetes Interventional Assessment of Slimming or Training to Lessen Inconspicuous Cardiovascular Dysfunction. The Diastolic Study
Study Start Date : October 2, 2015
Actual Primary Completion Date : August 31, 2018
Estimated Study Completion Date : August 2028

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
No Intervention: Standard Care
The Standard Care group will be contacted weekly (where possible) to reinforce cognitive behavioural adaptations and encourage compliance to diet and exercise. They will be provided with standard lifestyle advice according to NICE guidance.
Experimental: Total Dietary Replacement

Group receives a total meal replacement diet from Cambridge Weight Plan containing 810 kcal/day (40% protein, 50% carbohydrate, 10% fat). The diet will be stopped, and a maintenance diet re-introduced once 50% excess body weight has been lost, or by 12 weeks, whichever comes first.

The TDR will be undertaken alongside health behaviour coaching and relapse prevention contact & current medications will need to be adjusted initially and throughout the study.

Dietary Supplement: Cambridge Weight Plan

Group receives a total meal replacement diet from Cambridge Weight Plan containing 810 kcal/day (40% protein, 50% carbohydrate, 10% fat). As 3 or 4 mini-meals daily in flavoured formula food packets made up with water, milk or non-dairy alternative; or as snack bars based on preference. Supplemented with up to three portions of non-starchy vegetables and 2 litres of water, or other non-calorific drinks, per day. Participants to abstain from alcohol for study duration. The diet will be stopped, and a maintenance diet re-introduced once 50% excess body weight has been lost, or by 12 weeks, whichever comes first.

The TDR will be undertaken alongside health behaviour coaching and relapse prevention through weekly, where possible, contact (telephone or face-to-face) with a qualified dietician or equivalent.

Due to the potential risk of hypoglycaemia and symptomatic hypotension; medication at enrolment will need to be adjusted initially and throughout the study.


Experimental: Supervised Exercise

The exercise group will attend thrice weekly 60minute supervised exercise sessions at the Leicester-Loughborough Diet, Lifestyle and Physical Activity (LLP) BRU or at the Leicester Diabetes Centre. An initial assessment of cardiorespiratory fitness will be performed (VO2 max) to allow design of a tailored exercise programme.

Current medication will need to be adjusted initially and throughout the study.

Other: Supervised Exercise Sessions

The exercise group will attend supervised exercise sessions at the Leicester-Loughborough Diet, Lifestyle and Physical Activity (LLP) BRU or at the Leicester Diabetes Centre. The exercise program will typically consist of a thrice weekly, 60 minute session of moderate intensity aerobic exercise, in line with prevailing guidelines. An initial assessment of cardiorespiratory fitness will be performed, and exercise intensity titrated to aim for a workload of approximately 60% of the patient's VO2 max.

Due to the potential risk of hypoglycaemia and symptomatic hypotension; medication at enrolment will need to be adjusted initially and throughout the study.

Other Name: Physical Activity




Primary Outcome Measures :
  1. Increase in circumferential PEDSR rate as measured by CMR at 12 weeks. [ Time Frame: 12 weeks ]
    The aim of these analyses is to compare the primary outcome (diastolic strain rate) measured by CMR at 12 weeks between the TDR and standard care arms, and between the exercise and standard care arms. The primary analysis will be a per protocol analysis as this is a proof of principle study where we are primarily interested in the size of the treatment effect, rather than the practicability of the intervention.


Secondary Outcome Measures :
  1. Left ventricular mass [ Time Frame: Baseline, 4 and 12 weeks ]
    CMR to determine: structure and function

  2. End diastolic volume [ Time Frame: Baseline, 4 and 12 weeks ]
    CMR to determine: structure and function

  3. End systolic volume [ Time Frame: Baseline, 4 and 12 weeks ]
    CMR to determine: structure and function

  4. Ejection Fraction [ Time Frame: Baseline, 4 and 12 weeks ]
    CMR to determine: structure and function

  5. LA Volumes [ Time Frame: Baseline, 4 and 12 weeks ]
    CMR to determine: structure and function

  6. Myocardial Systolic strain (Circumferential & Longitudinal) [ Time Frame: Baseline, 4 and 12 weeks ]
    CMR to determine: structure and function

  7. Systolic Strain Rates [ Time Frame: Baseline, 4 and 12 weeks ]
    CMR to determine: structure and function

  8. Mean Ascending & Descending Aortic Distensibility [ Time Frame: Baseline, 4 and 12 weeks ]
    CMR to determine: arterial stiffness

  9. Pulse-wave velocity [ Time Frame: Baseline, 4 and 12 weeks ]
    CMR to determine: arterial stiffness

  10. Global Myocardial Perfusion Reserve [ Time Frame: Baseline, 4 and 12 weeks ]
    CMR to determine: structure and function, as a marker of vascular function

  11. Myocardial triglyceride content [ Time Frame: Baseline, 4 and 12 weeks ]
    CMR to determine: structure and function

  12. Liver triglyceride content [ Time Frame: Baseline, 4 and 12 weeks ]
    CMR to determine: structure and function

  13. Extracellular volume (ECV) [ Time Frame: Baseline, 4 and 12 weeks ]
    CMR to determine: structure and function, ECV as a marker of diffuse fibrosis

  14. Mitral Inflow Velocity [ Time Frame: Baseline, 4 and 12 weeks ]
    Echocardiography

  15. Myocardial Relaxation [ Time Frame: Baseline, 4 and 12 weeks ]
    Echocardiography

  16. Non-Invasive Marker of Left Ventricular Filling Pressure [ Time Frame: Baseline, 4 and 12 weeks ]
    Echocardiography

  17. Abdominal Subcutaneous (Deep) distribution [ Time Frame: 0 (consultation), 4 and 12 weeks ]
    MRI/CMR

  18. Abdominal Subcutaneous (Superficial) distribution [ Time Frame: 0 (consultation), 4 and 12 weeks ]
    MRI/CMR

  19. Adiposity (Total Body Fat) [ Time Frame: 0 (consultation), 4 and 12 weeks ]
    DEXA scan

  20. Adiposity (Fat Free Mass) [ Time Frame: 0 (consultation), 4 and 12 weeks ]
    DEXA scan

  21. Physical Fitness & activity (Peak VO2max) [ Time Frame: Baseline, 4 weeks and 12 weeks ]
    Cardiorespiratory fitness by incremental exercise testing (VO2max)

  22. Physical Fitness & activity (Accelerometer) [ Time Frame: Baseline, 4 weeks and 12 weeks ]
    Cardiorespiratory fitness by accelerometer for activity and sedentary time

  23. Family & Full Medical History [ Time Frame: Baseline ]
    diabetes diagnosis, duration, family history of CVD, diabetes type 1 & 2, stroke, myocardial infarction etc. Current medications.

  24. HbA1c [ Time Frame: Baseline, 4weeks, 12 weeks ]
    Biochemical Variables

  25. Fasting Glucose [ Time Frame: Baseline, 1 week, 2 week, 4weeks, 12 weeks ]
    Biochemical Variables

  26. Insulin [ Time Frame: Baseline, 4weeks, 12 weeks ]
    Biochemical Variables

  27. Adiponectin [ Time Frame: Baseline, 4weeks, 12 weeks ]
    Biochemical Variables

  28. Leptin [ Time Frame: Baseline, 4weeks, 12 weeks ]
    Biochemical Variables

  29. Total Cholesterol [ Time Frame: Baseline, 4weeks, 12 weeks ]
    Biochemical Variables

  30. LDL (Low density lipoprotein) [ Time Frame: Baseline, 4weeks, 12 weeks ]
    Biochemical Variables

  31. HDL (High density lipoprotein) [ Time Frame: Baseline, 4weeks, 12 weeks ]
    Biochemical Variables

  32. Triglycerides [ Time Frame: Baseline, 4weeks, 12 weeks ]
    Biochemical Variables

  33. Liver Function Test (LFT) [ Time Frame: Baseline, 4weeks, 12 weeks ]
    Biochemical Variables

  34. Thyroid Function Tests (TFT) [ Time Frame: Baseline, 4weeks, 12 weeks ]
    Biochemical Variables

  35. Vitamin C [ Time Frame: Baseline, 4weeks, 12 weeks ]
    Biochemical Variables

  36. Vitamin D [ Time Frame: Baseline, 4weeks, 12 weeks ]
    Biochemical Variables

  37. Group B Vitamin Panel [ Time Frame: Baseline, 4weeks, 12 weeks ]
    Biochemical Variables

  38. Iron [ Time Frame: Baseline, 4weeks, 12 weeks ]
    Biochemical Variables

  39. Serum Ferritin [ Time Frame: Baseline, 4weeks, 12 weeks ]
    Biochemical Variables

  40. Full Blood Count (with Haematocrit) [ Time Frame: Baseline, 4weeks, 12 weeks ]
    Biochemical Variables

  41. B-Type Natriuretic Peptide (BNP) [ Time Frame: Baseline, 4weeks, 12 weeks ]
    Biochemical Variables

  42. Metabolomic and Inflammatory Markers [ Time Frame: Baseline, 4weeks, 12 weeks ]
    Biochemical Variables

  43. C-peptide [ Time Frame: Baseline, 4weeks, 12 weeks ]
    Biochemical Variables

  44. Height [ Time Frame: Baseline ]
    Standard Anthropometric Variables

  45. Weight [ Time Frame: Baseline, 1, 2, 4, 6, 8, 12 weeks, 26 weeks, 52 weeks ]
    Standard Anthropometric Variables, derivation of BMI

  46. Waist & Hip Circumference [ Time Frame: Baseline, 12 weeks ]
    Standard Anthropometric Variables

  47. Systolic and Diastolic BP [ Time Frame: Baseline, 1, 2, 4, 6, 8, 12 weeks, 26 weeks, 52 weeks ]
    Standard Anthropometric Variables

  48. Heart rate [ Time Frame: Baseline, 1, 2, 4, 6, 8, 12 weeks, 26 weeks, 52 weeks ]
    Standard Anthropometric Variables

  49. Hypoglycaemia [ Time Frame: Baseline, 4weeks, 12 weeks ]
    self reported in blood glucose monitoring/hypo diary

  50. 7-Point Profile Glucose Monitoring [ Time Frame: 0weeks, 4weeks, 12 weeks ]
    self reported in blood glucose monitoring/hypo diary

  51. Adverse Events [ Time Frame: Baseline, 1, 2, 4, 6, 8, 12 weeks ]
    Safety

  52. Food Diary [ Time Frame: Baseline, 12 weeks ]
    Self-reporting

  53. EQ5D Questionnaire [ Time Frame: Baseline, 12 weeks ]
    Questionnaire

  54. Exercise Questionnaire [ Time Frame: Baseline, 12 weeks ]
    Questionnaire



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Capacity to provide informed consent before any trial-related activities
  • Established T2DM (≥3months)
  • HbA1c ≤ 9% if on triple therapy or ≤ 10% on diet & exercise or monotherapy or dual therapy
  • Current glucose lowering therapy either mono, dual or triple of any combination of metformin, sulphonylurea, DPP-IV inhibitor, GLP-1 therapy or an SGLT2 +/- diet and exercise
  • Poorly managed diet controlled diabetes (with HbA1c > 6.5% , not currently taking any glucose lowering therapy, meeting BMI inclusion range)
  • Body mass index > 30Kg/m2 or > 27.5 Kg/m2 (South Asian),
  • Diagnosis of T2DM before the age of 60 years of age
  • Age ≥18 and ≤ 65 years

Exclusion Criteria:

  • • Diabetes duration >12 years
  • Currently taking more than three glucose lowering therapies
  • Weight-loss of >5kg in the preceding 6 months
  • Stage 4 or 5 chronic kidney disease (eGFR< 30ml/min/1.73m2),
  • Current therapy with Insulin, thiazolidinediones, steroids or atypical antipsychotic medication
  • Untreated thyroid disease
  • Known macrovascular disease including coronary artery disease, stroke/TIA or peripheral vascular disease
  • Presence of arrhythmia (including atrial fibrillation, atrial flutter, or 2nd or 3rd degree atrioventricular block)
  • Known heart failure
  • Other clinically relevant heart disease
  • Inability to exercise or undertake a MRP
  • Absolute contraindication to CMR
  • Cardiovascular symptoms (angina, limiting dyspnoea during normal physical activity)
  • Inflammatory condition e.g. Connective tissue disorder, Rheumatoid arthritis

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): NCT02590822


Locations
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United Kingdom
Glenfield Hospital (University Hospitals of Leicester NHS Trust)
Leicester, United Kingdom, LE3 9QP
Sponsors and Collaborators
University of Leicester
University Hospitals, Leicester
National Institute for Health Research, United Kingdom
Investigators
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Principal Investigator: Gerry Dr McCann, MD University of Leicester
Additional Information:
Publications of Results:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: University of Leicester
ClinicalTrials.gov Identifier: NCT02590822    
Other Study ID Numbers: 0498
182089 ( Other Identifier: NIHR Clinical Research Network )
First Posted: October 29, 2015    Key Record Dates
Last Update Posted: January 30, 2020
Last Verified: January 2020
Keywords provided by University of Leicester:
Diabetes
T2DM
young adults
heart
weight loss
MRI
exercise
diastolic function
Additional relevant MeSH terms:
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Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases