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

NCT03721874 | Completed Phase 4 DMC

• 1 other identifier: NL67170.068.18
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Prediabetic State; Substrate Oxidation

Keywords

Dapagliflozin; Disrupted glucose homeostasis; Nocturnal substrate oxidation; Glucose metabolism

Outcome Measures

Primary Outcomes (1)

• Change in nightly substrate oxidation measured as respiration quotient (RQ) during the sleeping period

  Comparison of dapagliflozin versus placebo after 14 days of treatment on nightly substrate oxidation as measured by respiratory quotient (VCO2/VO2) during the sleeping period.

  From screening to day 14

Secondary Outcomes (8)

• Change in morning and late afternoon hepatic glycogen content

  1 hour

• Change in 24h substrate oxidation as determined by indirect calorimetry in a whole-body respiratory chamber and based on urinary nitrogen excretion

  24 hours

• Change in 24h plasma markers

  24 hours

• Change in muscle mitochondrial function

  60 minutes

• Change in intrahepatic lipid content and composition

  45 minutes

Study Arms (2)

Dapagliflozin 10 mg

ACTIVE COMPARATOR

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.

Drug: Dapagliflozin 10mg

Placebo matching to dapagliflozin 10 mg

PLACEBO COMPARATOR

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

Drug: Placebo matching to Dapagliflozin 10 mg

Interventions

Dapagliflozin 10mg DRUG

The study consist of 2 weeks treatment period 1, 6-8 weeks wash-out period and 2 weeks treatment period 2. The subject may be administered dapagliflozin 10 mg during Period 1 or Period 2.

Dapagliflozin 10 mg

Placebo matching to Dapagliflozin 10 mg DRUG

The study consist of 2 weeks treatment period 1, 6-8 weeks wash-out period and 2 weeks treatment period 2. The subject may be administered placebo during Period 1 or Period 2.

Placebo matching to dapagliflozin 10 mg

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent prior to any study specific procedures.
• 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
• Body mass index (BMI) ≥ 27 and ≤ 38 kg/m2.
• Sedentary lifestyle (not more than 3 hours of programmed exercise per week).
• Stable dietary habits.
• 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%.

You may not qualify if:

• Clinical diagnosis of Type 1 or 2 Diabetes Mellitus.
• 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.
• Weight gain or loss \> 5 kg in the last 3 months, ongoing weight-loss diet (hypocaloric diet) or use of weight loss agents.
• Regular smoking and other regular nicotine use.
• Anaemia.
• Uncontrolled hypertension.
• 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.
• Unstable or rapidly progressing renal disease or estimated Glomerular Filtration Rate (eGFR) \<60 mL/min (Cockcroft-Gault formula).
• Use of anti-coagulant treatment and other concomitant medication will be evaluated on a case to case basis with a general physician.
• Use of medication such as oral glucocorticoids, anti-estrogens or other medications that are known to markedly influence insulin sensitivity.
• Use of loop diuretics.
• Intake of dietary supplements except multi-vitamins and minerals.
• 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).
• Known hypersensitivity to dapagliflozin or any of the excipients of the product.
• For women only - currently pregnant (confirmed with positive pregnancy test) or breast-feeding.

Sponsors & Collaborators

• Maastricht University: lead
• AstraZeneca: collaborator

Study Sites (1)

Maastricht University and Medical Centre

Maastricht, Limburg, 6200 MD, Netherlands

Location

Related Publications (1)

• Veelen A, Andriessen C, Op den Kamp Y, Erazo-Tapia E, de Ligt M, Mevenkamp J, Jorgensen JA, Moonen-Kornips E, Schaart G, Esterline R, Havekes B, Oscarsson J, Schrauwen-Hinderling VB, Phielix E, Schrauwen P. Effects of the sodium-glucose cotransporter 2 inhibitor dapagliflozin on substrate metabolism in prediabetic insulin resistant individuals: A randomized, double-blind crossover trial. Metabolism. 2023 Mar;140:155396. doi: 10.1016/j.metabol.2022.155396. Epub 2022 Dec 30.

  PMID: 36592688 DERIVED

MeSH Terms

Conditions

Prediabetic State

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Patrick Schrauwen, Prof. dr.

  principle investigator

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Model Details: Double-Blind, Randomized, Phase IV, Mechanistic, Placebo-Controlled, Cross-Over, Single-Center Study

Study Record Dates

• First Submitted: October 23, 2018
• First Posted: October 26, 2018
• Study Start: April 30, 2019
• Primary Completion: June 29, 2021
• Study Completion: June 29, 2021
• Last Updated: August 19, 2021

Record last verified: 2021-08

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)