Role of BCAA in glucose homeostasis

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Maastricht University

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Trial duration

14 Apr 2025 → ongoing

Decision date (initial)

2023-07-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

The primary objective is to investigate if prolonged boosting of BCAA oxidation will substantially lower fasting plasma glucose levels in patients with T2D.

Secondary objectives 7

1. Insulin sensitivity
2. Muscle mitochondrial function
3. Whole-body metabolic flexibility
4. Energy status of the heart
5. Cardiac function
6. Cognitive function
7. Continuous glucose profile

Conditions and MedDRA coding

Type 2 diabetes

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 10

1. Patients are able to provide signed and dated written informed consent prior to any study specific procedures
2. Women are post-menopausal (defined as at least 1 year post cessation of menses) and aged ≥ 45 and ≤ 76 years. Males are aged ≥ 40 years and ≤ 76 years
3. Patients should have suitable veins for cannulation or repeated venipuncture
4. Caucasians
5. BMI: 25-38 kg/m2
6. Diagnosed with T2D at least 1.5 years before the start of the study
7. Relatively well-controlled T2D: HbA1c < 8.5%
8. Oral glucose lowering medication: metformin only or in combination with sulfonylurea agents and/or on stable dose of a DPPIV inhibitor treatment for at least the last 3 months
9. No signs of active diabetes-related co-morbidities like active cardiovascular diseases, active diabetic foot, polyneuropathy or retinopathy
10. No signs of active liver or kidney malfunction

Exclusion criteria 8

1. Previous enrolment in a clinical study with an investigational product during the last 3 months or as judged by the Investigator
2. Participate in physical activity more than 3 times a week
3. Unstable body weight (weight gain or loss > 5 kg in the last three months)
4. Insulin dependent T2D
5. Patients with congestive heart failure and and/or severe renal and or liver insufficiency or known sodium retention with oedema
6. Patients using Probalan (probenecid), Haldol (haloperidol), Depakene (valproate) or medical products containing corticosteroids
7. Men: Hb <8.4 mmol/L, Women: Hb <7.8 mmol/l
8. Any contra-indication MRI scanning. These contra-indications include patients with e.g. the following: • Central nervous system aneurysm clip • Implanted neural stimulator • Implanted cardiac pacemaker of defibrillator • Cochlear implant • Metal containing corpora aliena in the eye or brains

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Glucose levels will be measured after an overnight fast expressed in mmol/l.

Secondary endpoints 7

1. Glucose clearance in ml/kg determined during an OGTT
2. O2-flux in pmol/mg/s measured with high resolution respirometry
3. Endogenous nsulin-stimulated change in respiratory exchange ratio (RER) with use of indirect calorimetry during the OGTT
4. PCr/ATP-ratio determined with phosphorus magnetic resonance spectroscopy
5. Cardiac function will be measured in 2 ways: 1) ejection fraction (microL) with use of cine-MRI 2) diastolic cardiac function with use of ultrasound (transthoracic echocardiography) and will be assessed with the following parameters: • Left atrial maximum volume (ml) • Peak E-wave velocity (cm/sec) • Peak A-wave velocity (cm/sec) • Pulsed wave TDI e’velocity (cm/sec) at lateral and septal basal regions • Tricuspid regurgitation systolic jet velocity (m/sec)
6. Cognitive function will be assessed in 2 ways: 1) Use of CANTAB 2) Questionnaires (Beck’s Depression Inventory and Pittsburgh Sleep Quality Index)
7. Continuous glucose profile will be measure with use of the CGM sensor

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Maastricht University

Sponsor organisation

Maastricht University

Address

P. O. Box 616

City

Maastricht

Postcode

6200

Country

Netherlands

Scientific contact point

Organisation

Maastricht University

Contact name

Dr. Esther Phielix

Public contact point

Organisation

Maastricht University

Contact name

Dr. Esther Phielix

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 25 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications