Effects of GABAA Receptor Modulation by AP-325 on Insulin Secretion in Patients with Type 2 Diabetes
- Registration Number
- NCT05160272
- Lead Sponsor
- The Deutsche Diabetes Forschungsgesellschaft e.V.
- Brief Summary
The aim of this single-center, prospective, randomized, double-blind, placebo-controlled, 2-arm parallel-group interventional study is to investigate the effect of 4-week treatment with AP-325 on C-peptide release as measure of insulin secretion compared to placebo in type 2 diabetes (T2D) patients.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 38
- Diagnosis of T2D
- Age between 25 and 75 years
- HbA1c ≥6.5 and ≤9.5 %
- BMI ≤ 45 kg/m2
- Treatment-naive or stable antihyperglycemic therapy with metformin, α-glucosidase-inhibitor and/or SGLT2 inhibitor
- Ability to give consent
- Acute infections (hsCRP > 5mg/dl, body temperature >37.5°C)
- Insulin therapy or treatment with sulfonylureas, glinides, GLP-1 receptor agonists, thiazolidinediones; current treatment with DPP-4 inhibitors or during the 4 weeks prior to baseline examination
- Uncontrolled hyperglycemia, e.g. fasting blood glucose >240 mg/dl
- Heart rate <50 or >100 beats per minute; systolic blood pressure <100 or >160 mmHg; diastolic blood pressure <50 or >100 mmHg; uncontrolled hypertension
- Creatinine clearance <60 ml/min (eGFR by MDRD formula)
- Severe chronic illnesses, such as congestive heart failure (NYHA III/IV), liver insufficiency (Child-Pugh Class B/C), history of acute coronary syndrome, stroke
- Anemia (Hb <12 g/l for men, Hb <11 g/l for women)
- Participation in another intervention study within 2 months before the examination
- Hypersensitivity against AP-325, placebo or other ingredients of IMP
- Immunocompromising diseases
- Immunomodulatory drugs (e.g. oral cortisone preparations, biologicals)
- Thyroid diseases with an unstable metabolic state (change in L-thyroxine dose within the past 6 weeks, TSH and fT4 outside the normal range)
- Planned pregnancy, pregnant or lactating women, positive pregnancy test, and woman of childbearing potential not using two adequate methods of contraception, including a barrier method and a highly efficacious non-barrier method
- Past (≤ 5 years) or current history of psychiatric disorders, including psychiatric depression
- HIV, hepatitis B or C disease
- Previous / current alcohol and / or drug abuse
- Malignant cancer
- BIA and MR-incompatible metal or magnetic implants, devices or objects inside of or on the body, claustrophobia
- Treatment with the following drug groups or agents:
Anticoagulant drugs (exception: acetylsalicylic acid 100 mg/day), dihydropyridines (e.g. nifedipine, amlodipine), azilsartan, losartan and irbesartan, celecoxib; if applicable, other drugs that are predominantly metabolized by CYP2C9
- Inhibitors or inducers of CYP2C9, CYP3A4, such as amiodarone, verapamil, rifampicin
- Poor CYP2C9 metabolizer
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Treatment Placebo matching AP-325 Placebo matching AP-325 film-coated tablet, once daily AP-325 Treatment AP-325 AP-325, film-coated tablet, 50mg once daily
- Primary Outcome Measures
Name Time Method Circulating C-peptide by iAUC of C-peptide during an IVGTT 4 weeks Change in circulating C-peptide levels from baseline to end of intervention measured by iAUC of C-peptide during an IVGTT until 60th minute (second phase) with AP-325 compared to placebo
- Secondary Outcome Measures
Name Time Method iAUC of circulating insulin (AIR) (first 10 min) 4 weeks Change in iAUC of circulating insulin (AIR) during an IVGTT in the first 10 minutes from baseline to end of treatment
iAUC of C-peptide level (overall) 4 weeks Change in C-peptide level during an IVGTT from baseline to end of treatment
disposition index (DI) 4 weeks Change in the disposition index (DI) through Minimal Model during an IVGTT from baseline to end of treatment
Ctrough-ss (Day 28) and the change from baseline to Day 28 4 weeks Change in relationship between Ctrough-ss (Day 28) and the change from baseline to Day 28 in primary and secondary endpoints
fructosamine levels III 4 weeks Change in fasting blood glucose from baseline to end of treatment
Plasma concentrations of AP-325 4 weeks Change in Plasma concentrations of AP-325 at 1 hour post-dose on Days 1 and 28; pre-dose on Days 4 and 28. Accumulation of Ctrough from Day 4 to Day 28
Basal insulin level 4 weeks Change in basal insulin level from baseline to end of treatment
C-peptide level 4 weeks Change in C-peptide level from baseline to end of treatment
Glucose level 4 weeks Change in glucose level from baseline to end of treatment
iAUC of glucose level (overall) 4 weeks Change in iAUC of glucose level during an IVGTT from baseline to end of treatment
fructosamine levels 4 weeks Change in 1.5-Anhydroglucitol glucose from baseline to end of treatment
iAUC of circulating insulin (overall) 4 weeks Change in iAUC of circulating insulin during an IVGTT from baseline to end of treatment
iAUC of C-peptide (first 10 min) 4 weeks Change in iAUC of C-peptide during an IVGTT in the first 10 minutes from baseline to end of treatment
iAUC of glucose (first 10 min) 4 weeks Change in iAUC of glucose during an IVGTT in the first 10 minutes from baseline to end of treatment
insulin secretion rate (ISR) 4 weeks Change in insulin secretion rate (ISR) during an IVGTT from baseline to end of treatment
fructosamine levels II 4 weeks Change in fructosamine level from baseline to end of treatment
peak insulin response 4 weeks Change in peak insulin response during an IVGTT from baseline to end of treatment
Trial Locations
- Locations (1)
German Diabetes Center
🇩🇪Duesseldorf, NRW, Germany