Clinical trial NCT05160272: Effects of GABAA Receptor Modulation by AP-325 on Insulin Secretion in Patients with Type 2 Diabetes
Official title: Effects of GABAA Receptor Modulation by AP-325 on Insulin
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Type2 Diabetes
Keywords: Type 2 Diabetes
Diabetes mellitus
GABAA receptor
β-cell function
glycemic control
Lead sponsor: German Diabetes Center
Sponsor class: OTHER
Collaborators: name: Algiax Pharmaceuticals GmbH
First posted: 2021-12-16
Enrollment: 38
Sex: ALL
Minimum age (years): 25
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Circulating C-peptide by iAUC of C-peptide during an IVGTT
timeFrame: 4 weeks
Secondary outcomes:
measure: Basal insulin level
timeFrame: 4 weeks
measure: C-peptide level
timeFrame: 4 weeks
measure: Glucose level
timeFrame: 4 weeks
measure: iAUC of circulating insulin (overall)
timeFrame: 4 weeks
measure: iAUC of C-peptide level (overall)
timeFrame: 4 weeks
measure: iAUC of glucose level (overall)
timeFrame: 4 weeks
measure: iAUC of circulating insulin (AIR) (first 10 min)
timeFrame: 4 weeks
measure: iAUC of C-peptide (first 10 min)
timeFrame: 4 weeks
measure: iAUC of glucose (first 10 min)
timeFrame: 4 weeks
measure: disposition index (DI)
timeFrame: 4 weeks
measure: peak insulin response
timeFrame: 4 weeks
measure: insulin secretion rate (ISR)
timeFrame: 4 weeks
measure: fructosamine levels
timeFrame: 4 weeks
measure: fructosamine levels II
timeFrame: 4 weeks
measure: fructosamine levels III
timeFrame: 4 weeks
measure: Plasma concentrations of AP-325
timeFrame: 4 weeks
measure: Ctrough-ss (Day 28) and the change from baseline to Day 28
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Duesseldorf
country: Germany
facility: German Diabetes Center
state: NRW
Study officials:
affiliation: Deutsches Diabetes-Zentrum
name: Michael Roden, MD
role: PRINCIPAL_INVESTIGATOR
References: