Effects of 2 Weeks Treatment With Dapagliflozin in Subjects With an Impaired Glucose Homeostasis on Nocturnal Substrate Oxidation (MaasFlex)

Maastricht University

Status and phase: Completed; Phase 4

Conditions: Prediabetic State; Substrate Oxidation

Treatments: Drug: Dapagliflozin 10mg; Drug: Placebo matching to Dapagliflozin 10 mg

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT03721874

NL67170.068.18

Details and patient eligibility

About

The purpose of this study is to investigate the effect of 2 weeks dapagliflozin treatment in individuals with a disrupted glucose homeostasis on the switch between carbohydrate and lipid oxidation during the night

Full description

To investigate if dapagliflozin improves nocturnal substrate oxidation expressed as respiration quotient (RQ) during the sleeping period in comparison with placebo after 2-weeks double blind treatment in subjects with a disrupted glucose homeostasis.

Enrollment: 16 patients

Sex: All

Ages: 40 to 75 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Provision of signed and dated informed consent prior to any study specific procedures.

2. Males aged ≥ 40 and ≤ 75 years and post-menopausal women (defined as at least 1 year post cessation of menses) aged ≥ 50 and ≤ 75 years

3. Body mass index (BMI) ≥ 27 and ≤ 38 kg/m2.

4. Sedentary lifestyle (not more than 3 hours of programmed exercise per week).

5. Stable dietary habits.

6. Impaired glucose homeostasis based on one or a combination of the following criteria:

   • Impaired Glucose Tolerance (IGT): plasma glucose values ≥ 7.8 mmol/l and ≤ 11.1 mmol/l 120 minutes after consumption of the glucose drink during the 2h, 3-point OGTT.
   • Impaired Fasting Glucose (IFG): fasting plasma glucose ≥ 6.1 mmol/l and ≤ 6.9 mmol/l.
   • Insulin Resistance: glucose clearance rate ≤ 360 ml/kg/min, as calculated by Oral Glucose Insulin Sensitivity 120 (OGIS120) model based on the 2h, 3-point OGTT.
   • HbA1c ≥ 5.7% and ≤ 6.4%.

Exclusion criteria

1. Clinical diagnosis of Type 1 or 2 Diabetes Mellitus.
2. Active cardiovascular disease: participants who experienced a heart attack in the last year, or participants who are currently under regular control of a physician for a heart condition.
3. Weight gain or loss > 5 kg in the last 3 months, ongoing weight-loss diet (hypocaloric diet) or use of weight loss agents.
4. Regular smoking and other regular nicotine use.
5. Anaemia.
6. Uncontrolled hypertension.
7. Clinically significant out of range values of serum levels of either alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) in the Investigator's opinion.
8. Unstable or rapidly progressing renal disease or estimated Glomerular Filtration Rate (eGFR) <60 mL/min (Cockcroft-Gault formula).
9. Use of anti-coagulant treatment and other concomitant medication will be evaluated on a case to case basis with a general physician.
10. Use of medication such as oral glucocorticoids, anti-estrogens or other medications that are known to markedly influence insulin sensitivity.
11. Use of loop diuretics.
12. Intake of dietary supplements except multi-vitamins and minerals.
13. Alcohol consumption of > 14 drinks per week for women and > 21 drinks per week for men (1 drink = 35 cl beer, 14 cl wine or 4 cl hard liquor).
14. Known hypersensitivity to dapagliflozin or any of the excipients of the product.
15. For women only - currently pregnant (confirmed with positive pregnancy test) or breast-feeding.
16. Participation in another biomedical study within 1 month before the screening visit.
17. Any contraindication for MRI scanning.
18. Participants who do not want to be informed about unexpected medical findings, or do not wish that their physician be informed about coincidental findings, cannot participate in the study.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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16 participants in 2 patient groups, including a placebo group

Dapagliflozin 10 mg

Active Comparator group

Description:

Patients will receive dapagliflozin 10 mg in tablet for a maximum of 14 days based on randomization sequence in Period 1. Patients that received 10 mg dapagliflozin in the first treatment period will receive matching placebo in the second treatment period for a maximum of 14 days.

Treatment:

Drug: Dapagliflozin 10mg

Placebo matching to dapagliflozin 10 mg

Placebo Comparator group

Description:

Patients will receive matching placebo in tablet for a maximum of 14 days based on randomization sequence. Patients who received placebo in the first treatment will receive 10 mg dapagliflozin in the second treatment period, for a maximum of 14 days

Treatment:

Drug: Placebo matching to Dapagliflozin 10 mg