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| Name | Class |
|---|---|
| AstraZeneca | INDUSTRY |
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
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| 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 |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in morning and late afternoon hepatic glycogen content | Comparison of dapagliflozin versus placebo after 14 days of treatment on hepatic glycogen content determined by non-invasive 13C-MRS (magnetic resonance spectroscopy) in the morning and evening | 1 hour |
| Change in 24h substrate oxidation as determined by indirect calorimetry in a whole-body respiratory chamber and based on urinary nitrogen excretion |
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Inclusion Criteria:
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:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Patrick Schrauwen, Prof. dr. | principle investigator | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Maastricht University and Medical Centre | Maastricht | Limburg | 6200 MD | Netherlands |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36592688 | Derived | 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. |
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Double-Blind, Randomized, Phase IV, Mechanistic, Placebo-Controlled, Cross-Over, Single-Center Study
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| 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. |
|
Comparison of dapagliflozin versus placebo after 14 days of treatment on 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 | Comparison of dapagliflozin versus placebo after 14 days of treatment on 24h plasma markers including plasma glucose, NEFA, total amino acid levels incl BCAA levels, insulin and glucagon | 24 hours |
| Change in muscle mitochondrial function | Comparison of dapagliflozin versus placebo after 14 days of treatment on muscle mitochondrial function as determined by high resolution respirometry | 60 minutes |
| Change in intrahepatic lipid content and composition | Comparison of dapagliflozin versus placebo after 14 days of treatment on intrahepatic lipid content and composition as determined by non-invasive 1H-MRS (magnetic resonance spectroscopy ) | 45 minutes |
| Change in intramyocellular lipid content and composition - including acylcarnitine levels | Comparison of dapagliflozin versus placebo after 14 days of treatment on intramyocellular lipid content and composition-including acylcarnitine levels as determined in muscle biopsies | 45 minutes |
| Change in muscle glycogen content | Comparison of dapagliflozin versus placebo after 14 days of treatment on muscle glycogen content as determined biochemically in muscle biopsies | 45 minutes |
| Change in systolic and diastolic blood pressure | Comparison of dapagliflozin versus placebo after 14 days of treatment on systolic and diastolic blood pressure | 45 minutes |
| ID | Term |
|---|---|
| D011236 | Prediabetic State |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| C529054 | dapagliflozin |
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