A Phase 1 interventional study of Metformin and Caffeine in Diabetes Mellitus, Type 2, sponsored by University of Southern Denmark. Terminated at 1 site in Denmark. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2022-06-16.
Sponsored by University of Southern Denmark · Phase 1, Interventional, and Other
Type 2 diabetes is a major public health concern. It is widely established that type 2 diabetes in linked to activated innate immunity and increased levels of C-reactive protein and interleukin-6 (IL-6) in plasma. Studies in humans and in liver cells has shown that IL-6 downregulates important drug metabolizing enzymes in the liver (cytochrome P450 (CYP) enzymes). More than half of the most prescribed drugs are eliminated by biotransformation of these enzymes.
The investigators have previously shown that initiating glucose-lowering treatment (e.g. metformin, sulphonylureas and insulin) leads to decreased therapeutic efficacy of the blood-thinning vitamin-K antagonist warfarin. Due to the non-specific effect of glucose lowering drugs, the investigators hypothesize that this is caused by the glucose-lowering effect rather than drug-drug interactions caused by the individual drugs.
Based on the proposal that reversal of increased plasma glucose affects drug metabolism, the investigators will perform a clinical pharmacokinetic trial. The purpose of the study is to elucidate whether initiation of glucose-lowering treatment causes altered drug metabolism among patients with type 2 diabetes. The study will include newly diagnosed and untreated type 2 diabetes patients who will ingest a 6-drug cocktail consisting of probes for specific CYP enzymes. Plasma and urine will be drawn over 6 hours to determine concentrations of the drugs and their metabolites. Patients will then initiate metformin treatment and to assess both short- and long-term impact of glucose-lowering, the same 6-drug cocktail will be ingested, and concentrations measured, after three weeks and three months. To help understand the mechanism and the putative involvement of inflammation, markers of inflammation such as cytokines, transcription factors, etc. will also be assesses.
9,589 studies on the registry are indexed under Diabetes Mellitus, Type 2; 1,332 are open to participants now.
This study's enrollment of 10 is below the median of 81 across 7,713 interventional studies indexed under Diabetes Mellitus, Type 2.
Browse Diabetes Mellitus, Type 2 studies →University of Southern Denmark is the lead sponsor of 335 studies on the registry; 45 are open to participants now.
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Patients will receive metformin 1000-2000 mg daily for 12 weeks.
Drug: Metformin · Drug: Caffeine · Drug: Efavirenz · Drug: Losartan · Drug: Omeprazol · Drug: Metoprolol · Drug: Midazolam
500 mg tablet
Also known as: Glucose lowering treatment
As part of a 6-drug cocktail caffeine 100 mg tablet will be administered as a single dose before the initiation of metformin treatment and 3 weeks and 12 weeks after. The drug will be used as a probe to assess CYP1A2 activity.
As part of a 6-drug cocktail efavirenz 50 mg coated tablet will be administered as a single dose before the initiation of metformin treatment and 3 weeks and 12 weeks after. The drug will be used as a probe to assess CYP2B6 activity.
As part of a 6-drug cocktail losartan 12.5 mg coated tablet will be administered as a single dose before the initiation of metformin treatment and 3 weeks and 12 weeks after. The drug will be used as a probe to assess CYP2C9 activity.
As part of a 6-drug cocktail Omeprazol 10 mg enteric-coated tablet will be administered as a single dose before the initiation of metformin treatment and 3 weeks and 12 weeks after. The drug will be used as a probe to assess CYP2C19 activity.
As part of a 6-drug cocktail metoprolol 12.5 mg release tablet will be administered as a single dose before the initiation of metformin treatment and 3 weeks and 12 weeks after. The drug will be used as a probe to assess CYP2D6 activity.
As part of a 6-drug cocktail midazolam 2 mg oral solution will be administered as a single dose before the initiation of metformin treatment and 3 weeks and 12 weeks after. The drug will be used as a probe to assess CYP3A4 activity.
Change from Baseline in Metabolic Rate of Midazolam (CYP3A4) at Week 3.
Change in activity of the drug metabolizing enzyme CYP3A4 following treatment with the glucose lowering drug metformin in 3 weeks. Assessment of the change is based on a change in the metabolic rate, which is the ratio between the concentration of midazolam and its primary metabolite is plasma (Probe drug for CYP3A4).
Time frame: Baseline and Week 3.
Change from Baseline in Metabolic Rate of Midazolam (CYP3A4) at Week 12.
Change in activity of the drug metabolizing enzyme CYP3A4 following treatment with the glucose lowering drug metformin in 12 weeks. Assessment of the change is based on a change in the metabolic rate, which is the ratio between the concentration of midazolam and its primary metabolite is plasma (Probe drug for CYP3A4).
Time frame: Baseline and Week 12.
Change from Baseline in Metabolic Rate of Caffeine (CYP1A2) at Week 3.
Change in activity of the drug metabolizing enzymes CYP1A2 following treatment with the glucose lowering drug metformin after 3 weeks. The change in activity is based on the metabolic rate for the probe drug caffeine.
Time frame: Baseline and Week 3.
Change from Baseline in Metabolic Rate of Caffeine (CYP1A2) at Week 12.
Change in activity of the drug metabolizing enzymes CYP1A2 following treatment with the glucose lowering drug metformin after 12 weeks. The change in activity is based on the metabolic rate for the probe drug caffeine.
Time frame: Baseline and Week 12.
Change from Baseline in Metabolic Rate of Efavirenz (CYP2B6) at Week 3.
Change in activity of the drug metabolizing enzymes CYP2B6 following treatment with the glucose lowering drug metformin after 3 weeks. The change in activity is based on the metabolic rate for the probe drug Efavirenz.
Time frame: Baseline and Week 3.
Change from Baseline in Metabolic Rate of Efavirenz (CYP2B6) at Week 12.
Change in activity of the drug metabolizing enzymes CYP2B6 following treatment with the glucose lowering drug metformin after 12 weeks. The change in activity is based on the metabolic rate for the probe drug Efavirenz.
Time frame: Baseline and Week 12.
Change from Baseline in Metabolic Rate of Losartan (CYP2C9) at Week 3.
Change in activity of the drug metabolizing enzymes CYP2C9 following treatment with the glucose lowering drug metformin after 3 weeks. The change in activity is based on the metabolic rate for the probe drug Losartan.
Time frame: Baseline and Week 3.
Change from Baseline in Metabolic Rate of Losartan (CYP2C9) at Week 12.
Change in activity of the drug metabolizing enzymes CYP2C9 following treatment with the glucose lowering drug metformin after 12 weeks. The change in activity is based on the metabolic rate for the probe drug Losartan.
Time frame: Baseline and Week 12.
Change from Baseline in Metabolic Rate of Omeprazole (CYP2C19) at Week 3.
Change in activity of the drug metabolizing enzymes CYP2C19 following treatment with the glucose lowering drug metformin after 3 weeks. The change in activity is based on the metabolic rate for the probe drug Omeprazole.
Time frame: Baseline and Week 3.
Change from Baseline in Metabolic Rate of Omeprazole (CYP2C19) at Week 12.
Change in activity of the drug metabolizing enzymes CYP2C19 following treatment with the glucose lowering drug metformin after 12 weeks. The change in activity is based on the metabolic rate for the probe drug Omeprazole.
Time frame: Baseline and Week 12.
Change from Baseline in Metabolic Rate of Metoprolol (CYP2D6) at Week 3.
Change in activity of the drug metabolizing enzymes CYP2D6 following treatment with the glucose lowering drug metformin after 3 weeks. The change in activity is based on the metabolic rate for the probe drug Metoprolol.
Time frame: Baseline and Week 3.
Change from Baseline in Metabolic Rate of Metoprolol (CYP2D6) at Week 12.
Change in activity of the drug metabolizing enzymes CYP2D6 following treatment with the glucose lowering drug metformin after 12 weeks. The change in activity is based on the metabolic rate for the probe drug Metoprolol.
Time frame: Baseline and Week 12.
Change from Baseline in HbA1c at Week 3.
Change in the regulation of blood glucose over time assessed by HbA1c
Time frame: Baseline and Week 3.
Change from Baseline in HbA1c at Week 12.
Change in the regulation of blood glucose over time assessed by HbA1c
Time frame: Baseline and Week 12.
Change from Baseline in insulin resistance at Week 3.
An oral glucose tolerance test will be performed and glucose, insulin and c-peptide will be measured and combined by the Homeostatic Model Assessment (HOMA) to report insulin resistance.
Time frame: Baseline and Week 3.
Change from Baseline in insulin resistance at Week 12.
An oral glucose tolerance test will be performed and glucose, insulin and c-peptide will be measured and combined by the Homeostatic Model Assessment (HOMA) to report insulin resistance.
Time frame: Baseline and Week 12.
Change from Baseline in Interleukin-1-B at Week 3.
Change in patients inflammatory status assessed by measurement of Interleukin-1-B.
Time frame: Baseline and Week 3.
Change from Baseline in Interleukin-1-B at Week 12.
Change in patients inflammatory status assessed by measurement of Interleukin-1-B.
Time frame: Baseline and Week 12.
Change from Baseline in Interleukin-2 at Week 3.
Change in patients inflammatory status assessed by measurement of Interleukin-2.
Time frame: Baseline and Week 3.
Change from Baseline in Interleukin-2 at Week 12.
Change in patients inflammatory status assessed by measurement of Interleukin-2.
Time frame: Baseline and Week 12.
Change from Baseline in Interleukin-6 at Week 3.
Change in patients inflammatory status assessed by measurement of Interleukin-6.
Time frame: Baseline and Week 3.
Change from Baseline in Interleukin-6 at Week 12.
Change in patients inflammatory status assessed by measurement of Interleukin-6.
Time frame: Baseline and Week 12.
Change from Baseline in Interleukin-10 at Week 3.
Change in patients inflammatory status assessed by measurement of Interleukin-10.
Time frame: Baseline and Week 3.
Change from Baseline in Interleukin-10 at Week 12.
Change in patients inflammatory status assessed by measurement of Interleukin-10.
Time frame: Baseline and Week 12.
Change from Baseline in Interferon-a at Week 3.
Change in patients inflammatory status assessed by measurement of Interferon-a.
Time frame: Baseline and Week 3.
Change from Baseline in Interferon-a at Week 12.
Change in patients inflammatory status assessed by measurement of Interferon-a.
Time frame: Baseline and Week 12.
Change from Baseline in Interferon-B at Week 3.
Change in patients inflammatory status assessed by measurement of Interferon-B.
Time frame: Baseline and Week 3.
Change from Baseline in Interferon-B at Week 12.
Change in patients inflammatory status assessed by measurement of Interferon-B.
Time frame: Baseline and Week 12.
Change from Baseline in Interferon-y at Week 3.
Change in patients inflammatory status assessed by measurement of Interferon-y.
Time frame: Baseline and Week 3.
Change from Baseline in Interferon-y at Week 12.
Change in patients inflammatory status assessed by measurement of Interferon-y.
Time frame: Baseline and Week 12.
Change from Baseline in Tumor Necrosis Factor-a at Week 3.
Change in patients inflammatory status assessed by measurement of Tumor Necrosis Factor-a.
Time frame: Baseline and Week 3.
Change from Baseline in Tumor Necrosis Factor-a at Week 12.
Change in patients inflammatory status assessed by measurement of Tumor Necrosis Factor-a.
Time frame: Baseline and Week 12.
Change from Baseline in High Sensitivity C-Reactive Protein at Week 3.
Change in patients inflammatory status assessed by measurement of High Sensitivity C-Reactive Protein.
Time frame: Baseline and Week 3.
Change from Baseline in High Sensitivity C-Reactive Protein at Week 12.
Change in patients inflammatory status assessed by measurement of High Sensitivity C-Reactive Protein.
Time frame: Baseline and Week 12.
Plan to share: No — Individual participant data cannot be shared due to general data protection regulation (GDPR).
Ran from Sep 2020 to primary completion in May 2022, 20 months.
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This study is terminated, as verified in Jun 2022. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Metformin
University of Southern Denmark →