Evaluation of the Impact of Intensive Short-Term Drug Therapy in Patients With Type 2 Diabetes Mellitus

Study Overview
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Brief Summary
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This phase IV study is a prospective open-label multi-center study to investigate the effect of a temporary individualized poly-pharmaceutical De-escalation treatment with the target to regenerate ß-cell function over 12 weeks on the disease stage and glycemic control in patients with type 2 diabetes. This is an uncontrolled pilot study to collect data for later confirmatory trials.

Detailed Description
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During the screening visit the patient will arrive at the study site and written informed consent will be obtained by the investigator. Inclusion and exclusion criteria will be controlled and blood will be drawn for HbA1c, the efficacy and the safety parameters. A POCT pregnancy test will be conducted in women of childbearing age. Patient demographics and history will be collect and a physical examination will be performed. The patient will complete a QoL questionnaire and will receive training about the de-escalation therapy approach. After all necessary biomarker results of the screening visit are accessible for the selection of the De-escalation treatment the treatment initiation visit will be performed. During this visit the investigator will use these results to determine a most optimal personalized treatment combination for regeneration of the pancreatic ß-cells within the next three months. An ECG will be recorded and the patient will be informed about his/her personalized treatment and its execution. The patient will receive the drugs in the volume required until the next visit. During the next two visits the patient will arrive at the investigational site at the agreed time-point and information regarding potential adverse events will be collected. Vital signs will be measured, and blood will be drawn for assessment of the efficacy parameters. Information about hypoglycaemia will be collected, and the patient will receive drug supply that lasts until the next visit. The patient will be instructed to stop the anti-diabetic medication 3 days before the next visit. For the final visit (visit 5) the patient will arrive at the investigational site after an overnight fast and information regarding potential adverse events and hypoglycaemic events will be collected. Vital signs will be measured, and blood will be drawn for assessment of the efficacy parameters. An oral glucose challenge with 75 g of glucose will be conducted with blood draws for assessment of glucose and other biomarkers at time-points 0, 1h and 2h. The investigator will give a recommendation for the consecutive follow-up treatment requirements based on the results of the glucose challenge test. The patient will complete a QoL questionnaire (DTSQ) and this concludes study participation for the patient.

Official Title
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Pilot Study for Evaluation of the Impact of Intensive Short-Term Drug Therapy on Beta-Cell Function and Insulin Resistance in Patients With Type 2 Diabetes Mellitus

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Diabetes mellitus Type 2 De-escalation treatment (DET)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Informed consent obtained prior to any trial-related activities Male or female > 18 years Diagnosed with 2 Diabetes HbA1c <10% Current treatment with diet and exercise or up to two anti-diabetic drugs Exclusion Criteria: Patients participating in another investigational drug study Drug or alcohol abuse Pregnancy or breast feeding Sexually active woman of childbearing age not practicing accepted birth control Severe diabetes complications (in the discretion of investigator) Unstable significant cardiovascular disease with admission to emergency room or hospital in last 45 days Lack of compliance or other reason that in the discretion of the investigator precludes satisfactory participation in the study Any severe illness preventing participation in the study per protocol (in the discretion of the investigator)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: open-label, prospective, phase IV study
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: Diabetes mellitus Type 2 De-escalation treatment (DET)|All employed drugs are approved in the US for treatment of type 2 diabetes and are used within their label. There will be defined individual treatment drug combinations at an earlier stage of diabetes as in standard treatment. The DET combination will be composed out of one each or more of the drugs and interventions listed below. A. Relieve for the insulin-producing ß-cells insulin glargine (6 to 20 U at bedtime) insulin degludec (5 to 15 U at bedtime) B. Reduction of hormonal visceral lipid tissue activity/chronic inflammation Weight loss liraglutide (0.6 mg/day) exenatide (15 µg/day) C. Treatment of metabolic and vascular insulin resistance Pioglitazone (30 mg) D. Treatment of glucose toxicity Empagliflozin (SGLT-II inhibitor; 10 mg) Dapagliflozin (SGLTII-Inhibitor, 10 mg) Canagliflozin (SGLT-II inhibitor, 100 mg) Metformin (inhibition of hepatic glucose production, 500 mg) To avoid hypos, all drugs are initially given in the lowest possible dose.|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| impact of a temporary personalized poly-pharmaceutical treatment on the disease stage in patients with type 2 diabetes | combined drug application | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HbA1c measurement to evaluate the impact of the poly-pharmaceutical treatment on the glycemic control | venous blood draw to evaluate the HbA1c | 12 weeks | 
| RBP4 will be measured to evaluate the impact of the poly-pharmaceutical treatment on the RBP4 level | blood draw to measure the above mentioned biomarker | 12 weeks | 
| the biomarker adiponectin will be measured to evaluate the impact of the poly-pharmaceutical treatment on the adiponectin level | blood draw to measure the above mentioned biomarker | 12 weeks | 
| insulin, c-peptide, intact proinsulin, glucagon will be measured to evaluate the impact of a temporary personalized poly-pharmaceutical treatment on beta-cell function | blood draw to measure the above mentioned biomarkers | 12 weeks | 
| hsCRP, IL-6, angiopoetin 2 will be measured to evaluate the impact of a temporary personalized poly-pharmaceutical treatment on biomarkers of inflammation | blood draw to measure the above mentioned biomarkers | 12 weeks | 
| Questionnaire about the diabetes treatment satisfaction (DTSQ) will be filled by the patient to evaluate the impact of a temporary personalized poly-pharmaceutical treatment on the quality of Life | Questionnaire to be filled by study participant, the scale of the questionnaire reaches from 1 (very good) to 10 (very bad), all questions are bloning to the diabetes treatment. | 12 weeks | 
| Renal function | blood draw and urine sample to measure renal function, which will be evaluated with the following parameters creatinine, GFR, total protein (serum and urine), Uric acid and urea before and after the temporary personalized poly-pharmaceutical treatment | 12 weeks | 
| Liver function | blood draw to measure Liver function, which will be evaluated with the following parameters AST, ALT, gamma-GT, and alkaline phosphatase before and after the temporary personalized poly-pharmaceutical treatment | 12 weeks | 
| Heart function | blood draw to measure Heart function, which will be evaluated with the following parameters creatine kinase, and cK-MB before and after the temporary personalized poly-pharmaceutical treatment | 12 weeks | 
| Electrolytic balance | blood draw to measure Electrolytic balance, which will be evaluated with the following parameters: sodium, potassium and calcium before and after the temporary personalized poly-pharmaceutical treatment | 12 weeks |