Type 2 DiabetesPhase 4NaPB2NCT05836350
Role of BCAA in Glucose Homeostasis
A Phase 4 study testing 4.8 g/m^2/day NaPB in people with Type 2 Diabetes, run by Maastricht University.
Trial summary
This clinical trial study aims to evaluate the effects of prolonged NaPB treatment in a maximum of 20 patients with T2D. The primary objective is: to investigate if prolonged boosting of ing BCAA oxidation will substantially lower plasma glucose levels in patients with T2D. Read more about this study
- Who is it for?
- Ages 40 to 76 years
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- 4.8 g/m^2/day NaPB
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- No sites listed yet
- Study dates
- Jun 2023to May 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 76 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients are able to provide signed and dated written informed consent prior to any study specific procedures
- 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
- Patients should have suitable veins for cannulation or repeated venipuncture
- Caucasians
- BMI: 25-38 kg/m2
- Diagnosed with T2D at least 1.5 years before the start of the study
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- Relatively well-controlled T2D: HbA1c < 8.5%
- 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
- No signs of active diabetes-related co-morbidities like active cardiovascular diseases, active diabetic foot, polyneuropathy or retinopathy
- No signs of active liver or kidney malfunction
Who cannot join
- Previous enrolment in a clinical study with an investigational product during the last 3 months or as judged by the Investigator
- Participate in physical activity more than 3 times a week
- Unstable body weight (weight gain or loss > 5 kg in the last three months)
- Insulin dependent T2D
- Patients with congestive heart failure and and/or severe renal and or liver insufficiency or known sodium retention with oedema
- Patients using Probalan (probenecid), Haldol (haloperidol), Depakene (valproate) or medical products containing corticosteroids
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- Men: Hb <8.4 mmol/L, Women: Hb <7.8 mmol/l
- 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
Trial locations and contacts
No sites are listed yet.
Elnaz Daraei, MSc. contact
About this study
Official title: Targeting Branched-chain Amino Acid Oxidation to Improve Glycaemic Control in Patients With Type 2 Diabetes
This clinical trial study aims to evaluate the effects of prolonged NaPB treatment in a maximum of 20 patients with T2D. The primary objective is:
to investigate if prolonged boosting of ing BCAA oxidation will substantially lower plasma glucose levels in patients with T2D.
Read more
Participants will undergo a Clinical randomized controlled trial (RCT) with a double-blinded, placebo-controlled, cross-over design, including a wash-out period of 12 weeks. The trial will contain 2 treatment arms, with each a duration of 12 weeks.
Participants will have a 12-week oral administration of 4.8 g/m2/day NaPB (in the form of Pheburane) or placebo per day. Although depending on body surface area, ~21 g Pheburane needs to be administered spread over the day 3 times taken with a meal.
Read the detailed description
Several studies identified branched-chain amino acids (BCAA; leucine, isoleucine, and valine) to be substantially elevated in people with T2D, possibly caused by lower BCAA oxidation rates. Plasma BCAA levels are strongly associated with insulin resistance and other key metabolic disarrangements as seen in T2D, including mitochondrial function, liver fat content, and metabolic flexibility. We, recently, showed that stimulating BCAA oxidation for 2 weeks with sodium-phenylbutyrate (NaPB) treatment -a drug known to accelerate BCAA oxidation- decreased BCAA plasma levels in patients with T2D. This reduction in plasma BCAA levels was paralleled with a robust improvement in peripheral insulin sensitivity and muscle mitochondrial oxidative capacity. Interestingly, a strong tendency was found for lower fasting glucose levels, an indication of better glucose control. These findings form lead to further evaluating this treatment strategy to improve glucose homeostasis and lower hyperglycaemic conditions in patients with T2D. So far, this strategy has been tested only in several rodent models reporting promising, beneficial outcomes on glucose homeostasis and heart function.
The aim of the present study is to evaluate the effects of prolonged treatment: patients with T2D will undergo a 12-week NaPB intervention with the aim of substantially lower fasting plasma glucose levels. The outcomes of this project evaluate a novel strategy to treat patients with T2D.
- Conditions
- Type 2 Diabetes
- Being tested
- 4.8 g/m^2/day NaPB, 4.8 g/m^2/day placebo
- Keywords
- type 2 Diabetes, branched-chain amino acid metabolism, glucose homeostasis, sodium-phenylbutyrate, insulin resistance
- Medical subject headings
- Diabetes Mellitus, Type 2, Insulin Resistance
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
4.8 g/m^2/day NaPBDrug
Also called Pheburane, NaPB
12-week oral administration of 4.8 g/m^2/day NaPB (in the form of Pheburane) per day. Although depending on body surface area, ~21 g Pheburane needs to be administered spread over the day in 3 times taken with a meal.
4.8 g/m^2/day placeboDrug
Also called Placebo
12-week oral administration of 4.8 g/m^2/day NaPB (in the form of Pheburane) or placebo per day. Although depending on body surface area, ~21 g Pheburane needs to be administered spread over the day in 3 times taken with a meal.
| Study group | Role | What they receive |
|---|---|---|
| 4.8 g/m^2/day NaPB | Active comparator | 12-week oral administration of 4.8 g/m^2/day Sodium-phenylbutyrate (NaPB) (in the form of Pheburane) Receives: Drug: 4.8 g/m^2/day NaPB |
| 4.8 g/m^2/day Placebo | Placebo comparator | 12-week oral administration of 4.8 g/m2/day identical placebo granules. Receives: Drug: 4.8 g/m^2/day placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
fasting plasma glucose levels
Glucose levels will be measured after an overnight fast expressed in mmol/l.
Measured: at week 12 of each intervention period
Secondary outcomes (10)
whole-body insulin sensitivity
glucose clearance in ml/kg determined during an OGTT at 6 weeks glucose disposal rate (delta Rd) in umol/kg/min measured with the clamp at 12 weeks
Measured: at week 6 and week 12 of each intervention period
muscle mitochondrial function
O2-flux will be measured with high-resolution respirometry
Measured: at week 6 and week 12 of each intervention period
whole-body metabolic flexibility
insulin-stimulated change in respiratory exchange ratio will be determined with use of indirect calorimetry during the clamp
Measured: at week 12 of each intervention period
energy status of the heart
PCr/ATP-ratio will be determined with phosphorus magnetic resonance spectroscopy
Measured: at week 12 of each arm
cardiac function: ejection fraction
The cardiac function will be measured via ejection fraction (microL) with the use of cine-MRI
Measured: at week 12 of each arm
cardiac function: left atrial maximum volume
The cardiac function will be measured via diastolic cardiac function with the use of ultrasound (transthoracic echocardiography) with the following parameter: Left atrial maximum volume (ml)
Measured: at week 12 of each arm
cardiac function: peak A-wave velocity (cm/sec)
The cardiac function will be measured via diastolic cardiac function with the use of ultrasound (transthoracic echocardiography) with the following parameter: Peak A-wave velocity (cm/sec)
Measured: at week 12 of each arm
cardiac function: pulsed wave TDI velocity (cm/sec) at lateral and septal basal regions
The cardiac function will be measured via diastolic cardiac function with the use of ultrasound (transthoracic echocardiography) with the following parameter: Pulsed wave TDI velocity (cm/sec) at lateral and septal basal regions
Measured: at week 12 of each arm
cardiac function: peak E-wave velocity
The cardiac function will be measured via diastolic cardiac function with the use of of ultrasound (transthoracic echocardiography) will be assessed with the following parameters: Peak E-wave velocity (cm/sec)
Measured: at week 12 of each arm
cardiac function: tricuspid regurgitation systolic jet velocity
The cardiac function will be measured via diastolic cardiac function with the use of ultrasound (transthoracic echocardiography) with the following parameter: Tricuspid regurgitation systolic jet velocity (m/sec)
Measured: at week 12 of each arm
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 May 2023
- Study startJun 2023 (estimated)
- Primary completionOct 2025 (estimated)
- Study completionMay 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Clinical randomized controlled trial (RCT) with a double-blinded, placebo-controlled, cross-over design, including a wash-out period of 12 weeks. The trial will contain 2 treatment arms, with each a duration of 12 weeks.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Maastricht University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05836350
- Sponsor's protocol ID
- NaPB-2
- Acronym
- NaPB2
- Status last verified
- Apr 2023
- First submitted
- 7 Apr 2023
- Last updated
- 1 May 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Targeting Branched-chain Amino Acid Oxidation to Improve Glycaemic Control in Patients With Type 2 Diabetes
- ClinicalTrials.gov ID
- NCT05836350
- Acronym / sponsor ID
- NaPB2 / NaPB-2
- Conditions
- Type 2 Diabetes
- Keywords
- type 2 Diabetes, branched-chain amino acid metabolism, glucose homeostasis, sodium-phenylbutyrate, insulin resistance
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Maastricht UniversityUniversity, hospital or other
- Study start
- Jun 2023 (estimated)
- Primary completion
- Oct 2025 (estimated)
- Study completion
- May 2026 (estimated)
- First posted
- 1 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical trial study aims to evaluate the effects of prolonged NaPB treatment in a maximum of 20 patients with T2D. The primary objective is:
to investigate if prolonged boosting of ing BCAA oxidation will substantially lower plasma glucose levels in patients with T2D.
Participants will undergo a Clinical randomized controlled trial (RCT) with a double-blinded, placebo-controlled, cross-over design, including a wash-out period of 12 weeks. The trial will contain 2 treatment arms, with each a duration of 12 weeks.
Participants will have a 12-week oral administration of 4.8 g/m2/day NaPB (in the form of Pheburane) or placebo per day. Although depending on body surface area, ~21 g Pheburane needs to be administered spread over the day 3 times taken with a meal.
Detailed description
Several studies identified branched-chain amino acids (BCAA; leucine, isoleucine, and valine) to be substantially elevated in people with T2D, possibly caused by lower BCAA oxidation rates. Plasma BCAA levels are strongly associated with insulin resistance and other key metabolic disarrangements as seen in T2D, including mitochondrial function, liver fat content, and metabolic flexibility. We, recently, showed that stimulating BCAA oxidation for 2 weeks with sodium-phenylbutyrate (NaPB) treatment -a drug known to accelerate BCAA oxidation- decreased BCAA plasma levels in patients with T2D. This reduction in plasma BCAA levels was paralleled with a robust improvement in peripheral insulin sensitivity and muscle mitochondrial oxidative capacity. Interestingly, a strong tendency was found for lower fasting glucose levels, an indication of better glucose control. These findings form lead to further evaluating this treatment strategy to improve glucose homeostasis and lower hyperglycaemic conditions in patients with T2D. So far, this strategy has been tested only in several rodent models reporting promising, beneficial outcomes on glucose homeostasis and heart function.
The aim of the present study is to evaluate the effects of prolonged treatment: patients with T2D will undergo a 12-week NaPB intervention with the aim of substantially lower fasting plasma glucose levels. The outcomes of this project evaluate a novel strategy to treat patients with T2D.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Clinical randomized controlled trial (RCT) with a double-blinded, placebo-controlled, cross-over design, including a wash-out period of 12 weeks. The trial will contain 2 treatment arms, with each a duration of 12 weeks.
| Arm | Type | Receives |
|---|---|---|
| 4.8 g/m^2/day NaPB | Active comparator | Drug: 4.8 g/m^2/day NaPB12-week oral administration of 4.8 g/m^2/day Sodium-phenylbutyrate (NaPB) (in the form of Pheburane) |
| 4.8 g/m^2/day Placebo | Placebo comparator | Drug: 4.8 g/m^2/day placebo12-week oral administration of 4.8 g/m2/day identical placebo granules. |
Who may qualify
- Ages
- 40 to 76 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients are able to provide signed and dated written informed consent prior to any study specific procedures
- 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
- Patients should have suitable veins for cannulation or repeated venipuncture
- Caucasians
- BMI: 25-38 kg/m2
Key exclusion criteria (13 listed)
- Previous enrolment in a clinical study with an investigational product during the last 3 months or as judged by the Investigator
- Participate in physical activity more than 3 times a week
- Unstable body weight (weight gain or loss > 5 kg in the last three months)
- Insulin dependent T2D
- Patients with congestive heart failure and and/or severe renal and or liver insufficiency or known sodium retention with oedema
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 4.8 g/m^2/day NaPBAlso: Pheburane, NaPB12-week oral administration of 4.8 g/m^2/day NaPB (in the form of Pheburane) per day. Although depending on body surface area, ~21 g Pheburane needs to be administered spread over the day in 3 times taken with a meal. | Drug | 4.8 g/m^2/day NaPB |
| 4.8 g/m^2/day placeboAlso: Placebo12-week oral administration of 4.8 g/m^2/day NaPB (in the form of Pheburane) or placebo per day. Although depending on body surface area, ~21 g Pheburane needs to be administered spread over the day in 3 times taken with a meal. | Drug | 4.8 g/m^2/day Placebo |
Primary outcome
fasting plasma glucose levels
Time frame: at week 12 of each intervention period
Glucose levels will be measured after an overnight fast expressed in mmol/l.
10 secondary outcomes
whole-body insulin sensitivity
Time frame: at week 6 and week 12 of each intervention period
muscle mitochondrial function
Time frame: at week 6 and week 12 of each intervention period
whole-body metabolic flexibility
Time frame: at week 12 of each intervention period
energy status of the heart
Time frame: at week 12 of each arm
cardiac function: ejection fraction
Time frame: at week 12 of each arm
cardiac function: left atrial maximum volume
Time frame: at week 12 of each arm
cardiac function: peak A-wave velocity (cm/sec)
Time frame: at week 12 of each arm
cardiac function: pulsed wave TDI velocity (cm/sec) at lateral and septal basal regions
Time frame: at week 12 of each arm
cardiac function: peak E-wave velocity
Time frame: at week 12 of each arm
cardiac function: tricuspid regurgitation systolic jet velocity
Time frame: at week 12 of each arm
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elnaz Daraei, MSc. contact
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing 4.8 g/m^2/day NaPB in people with Type 2 Diabetes, run by Maastricht University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 1 May 2023. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Esther Phielix, PhD. (043- 388 1311, esther.phielix@maastrichtuniversity.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
fasting plasma glucose levels (time frame: at week 12 of each intervention period). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2023.