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The PRE-D Trial: Effect of Dapagliflozin, Metformin and Physical Activity in Pre-diabetes

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ClinicalTrials.gov Identifier: NCT02695810
Recruitment Status : Completed
First Posted : March 1, 2016
Last Update Posted : October 7, 2019
Sponsor:
Collaborators:
The Novo Nordic Foundation
Rigshospitalet, Denmark
AstraZeneca
Bayer
Information provided by (Responsible Party):
Kristine Færch, Steno Diabetes Center Copenhagen

Brief Summary:
The overall objective is to compare the short-term (3 months) effectiveness of three glucose-lowering interventions (dapagliflozin, metformin and physical activity) on glucose variability, body composition, and cardiometabolic risk factors in overweight or obese individuals with pre-diabetes (HbA1c 5.7-6.4% / 39-47 mmol/mol).

Condition or disease Intervention/treatment Phase
Prediabetic State Obesity Drug: Dapagliflozin Drug: Metformin Behavioral: Exercise Phase 2

Detailed Description:
Different medical therapies and lifestyle modification for the prevention of type 2 diabetes have yet to be compared head-to-head in individuals with pre-diabetes. This research project will compare different glucose-lowering interventions in overweight and obese individuals with HbA1c levels in the pre-diabetic range.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Effect of Dapagliflozin, Metformin and Physical Activity on Glucose Variability, Body Composition and Cardiovascular Risk in Pre-diabetes
Actual Study Start Date : February 24, 2016
Actual Primary Completion Date : September 20, 2018
Actual Study Completion Date : January 13, 2019


Arm Intervention/treatment
Experimental: Dapagliflozin
Dapagliflozin, 10 mg per day
Drug: Dapagliflozin
10 mg per day as monotherapy for 13 weeks
Other Name: Forxiga, AstraZeneca

Active Comparator: Metformin
Metformin, 2 x 850 mg per day
Drug: Metformin
2 x 850 mg per day as monotherapy for 13 weeks
Other Name: Aurobindo, Orion Pharma

Active Comparator: Exercise
Exercise, interval training
Behavioral: Exercise
Interval training, 5 times per week, 30 min per session

No Intervention: Control
No intervention



Primary Outcome Measures :
  1. Mean amplitude of glycaemic excursions (MAGE) as assessed by continuous glucose monitoring [ Time Frame: Change from baseline to 13 weeks and 26 weeks ]

Secondary Outcome Measures :
  1. Intra-day glycaemic variability as assessed by continuous overall net glycaemic action (CONGA) [ Time Frame: Change from baseline to 13 weeks and 26 weeks ]
  2. Daily time spent above different glucose concentrations ( e.g. >6.1 mmol/L, >7.0 mmol/L, >7.8 mmol/L, and >11.1 mmol/L) [ Time Frame: Change from baseline to 13 weeks and 26 weeks ]
  3. HbA1c [ Time Frame: Change from baseline to 13 weeks and 26 weeks ]
  4. Glucose concentrations during OGTT [ Time Frame: Change from baseline to 13 weeks and 26 weeks ]
  5. Insulin secretion as assessed by the insulinogenic index [ Time Frame: Change from baseline to 13 weeks and 26 weeks ]
  6. Insulin sensitivity as assessed by the insulin sensitivity index [ Time Frame: Change from baseline to 13 weeks and 26 weeks ]
  7. Body weight (kg) [ Time Frame: Change from baseline to 13 weeks and 26 weeks ]
  8. Body fat (%) as assessed by DEXA scan [ Time Frame: Change from baseline to 13 weeks and 26 weeks ]
  9. Cardiorespiratory fitness as assessed by maximal oxygen uptake (VO2 max) [ Time Frame: Change from baseline to 13 weeks and 26 weeks ]
  10. Respiratory exchange ratio (RER) as assessed by indirect calorimetry [ Time Frame: Change from baseline to 13 weeks and 26 weeks ]
  11. Basal metabolic rate (BMR) as assessed by indirect calorimetry [ Time Frame: Change from baseline to 13 weeks and 26 weeks ]
  12. Time spent sedentary and in moderate-to-vigorous physical activity intensity as assessed by accelerometer [ Time Frame: Change from baseline to 13 weeks and 26 weeks ]
  13. Systolic and diastolic blood pressure [ Time Frame: Change from baseline to 13 weeks and 26 weeks ]
  14. Plasma lipids [ Time Frame: Change from baseline to 13 weeks and 26 weeks ]
  15. Number of self-reported adverse events and side effects [ Time Frame: Change from baseline to 13 weeks and 26 weeks ]
  16. Self-rated health and quality of life as assessed by questionnaire [ Time Frame: Change from baseline to 13 weeks and 26 weeks ]
  17. Sleep habits as assessed by questionnaire [ Time Frame: Change from baseline to 13 weeks and 26 weeks ]
  18. Dietary intake as assessed by a food diary [ Time Frame: Change from baseline to 13 weeks and 26 weeks ]
  19. Adherence to the different interventions as assessed by number of tablets returned or number of training passes completed [ Time Frame: Change from baseline to 13 weeks and 26 weeks ]
  20. Responsiveness to interventions in individuals with different glucose tolerance status (impaired fasting glycaemia vs. impaired glucose tolerance) [ Time Frame: Change from baseline to 13 weeks and 26 weeks ]


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Ages Eligible for Study:   30 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • HbA1c: from ≥5.7% (39 mmol/mol) to ≤6.4% (47 mmol/mol)
  • Age: from ≥30 to ≤70 years of age
  • BMI ≥25 kg/m2

Exclusion Criteria:

  • Uncontrolled medical issues including but not limited to cardiovascular pulmonary, rheumatologic, hematologic, oncologic, infectious, gastrointestinal or psychiatric disease; diabetes or other endocrine disease; immunosuppression;
  • Current treatment with hormones which affect glucose metabolism;
  • Current treatment with loop diuretics or thiazolidinediones;
  • Current treatment with beta blockers or peroral steroids;
  • Bariatric surgery within the past 2 years;
  • Impaired renal function defined as an estimated GFR<60 ml/min/1.73m2;
  • Neurogenic bladder disorders;
  • Alcohol/drug abuse or in treatment with disulfiram (Antabus) at time of inclusion;
  • Pregnant or lactating women;
  • Fertile women not using birth control agents including oral contraceptives, gestagen injection, subdermal implants, hormonal vaginal ring, transdermal application, or intra-uterine devices;
  • Allergic to one or more of the medications used in the study;
  • Concomitant participation in other intervention study;
  • Unable to understand the informed consent and the study procedures.

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): NCT02695810


Locations
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Denmark
Steno Diabetes Center A/S
Gentofte, Denmark, 2820
Sponsors and Collaborators
Steno Diabetes Center Copenhagen
The Novo Nordic Foundation
Rigshospitalet, Denmark
AstraZeneca
Bayer
Investigators
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Principal Investigator: Marit E Jørgensen, PhD Steno Diabetes Center Copenhagen
Additional Information:
Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Kristine Færch, Senior Researcher, Steno Diabetes Center Copenhagen
ClinicalTrials.gov Identifier: NCT02695810    
Other Study ID Numbers: 2015-001552-30
First Posted: March 1, 2016    Key Record Dates
Last Update Posted: October 7, 2019
Last Verified: October 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Additional relevant MeSH terms:
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Prediabetic State
Diabetes Mellitus
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Metformin
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Hypoglycemic Agents
Physiological Effects of Drugs
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action