Effect of Glyceroltrinitrate on Human Energy Expenditure and Brown Adipose Tissue Thermogenesis

Brown Adipose Tissue Clinical Trial

— NEXT  

Official title:

Effect of Glyceroltrinitrate on Human Energy Expenditure and Brown Adipose Tissue Thermogenesis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05711199
• Other study ID #: NEXT Study
• Status: Recruiting
• Phase: Early Phase 1
• Start date: March 1, 2023
• Est. completion date: August 31, 2025

Study information

• Verified date: May 2024
• Source: University Hospital, Basel, Switzerland
• Contact: Matthias J Betz, MD
• Phone: 0041 61 556 56 54
• Email: matthias.betz[@]usb.ch
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The aim of this study is to evaluate the efficacy of glyceroltrinitrate (Nitroderm® TTS) to activate and expand human BAT as compared to mild cold exposure.

Description:

The activation of brown adipose tissue in response to glyceroltrinitrate as compared to cold exposure will be studied in an open-label, cross-over trial in healthy volunteers with random sequence of the two study periods (treatment and control) seperated by a washout period of 7 days.

In the treatment phase all participants will receive Nitroderm® TTS (glyceroltrinitrate) for a total of 15 days. For better tolerability, it will be will started with a lower dose of 5mg/24h (Nitroderm® TTS) the first 5 days and after that a change to Nitroderm® TTS 10mg/24h for another 10 days will be done. Each transdermal patch will be applied for 12 hours per day (overnight) to avoid development of nitrate tolerance.

Energy expenditure will be measured by indirect calorimetry before and after a mild cold exposure by placing a medical cooling system around their midsection. Additionally brown adipose tissue activity will determined by 18F-FDG-PET/CT 30 min after injection of 75 MBq of 18F-FDG. To analyse changes in BAT and muscle which are caused by glyceroltrinitrate as compared with cold stimulus, a tissue biopsie of supraclavicular BAT and skeletal muscle (musculus vastus lateralis) will be performed.

To measure changes in glucose tolerance and triglyceride levels a mixed meal test will be performed during control and treatment phase respectively. Additionally, a indirect calorimetry will be conducted before and after mixed meal test to assess diet-induced thermogenesis, i.e. the increase in REE due to ingestion of nutrients

In control phase the same examinations will be performed, but without glyceroltrinitrat.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: August 31, 2025
• Est. primary completion date: May 31, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• BMI 18.5 to 25 kg/m2 or 30 to 35kg/m2

• Able to give informed consent as documented by signature

• Age 18 to 40 years

Exclusion Criteria:

• Contraindications to glyceroltrinitrate, e.g. known hypersensitivity or allergy

• Concomitant medication: Non-steroidal anti-inflammatory drugs (NSAID), glucocorticoids, diuretics, antihypertensives, fibrates or statins, metformin, PDE-5-inhibitors

• Clinically significant concomitant disease states (e.g. renal failure, hepatic dysfunction, cardiovascular disease, diabetes mellitus)

• Hypersensitivity to cold (e.g. Raynaud Syndrome)

• Orthostatic hypotension: systolic blood pressure decreases min. 20mmHg or diastolic blood pressure decreases min 10mmHg within 3-5min after standing up (Schellong Test at screening visit)

• History of orthostatic syncope or pre-syncope

• Blood pressure values below 100 mmHg systolic and 60 mmHg diastolic

• Allergy to local anesthetic

• Hypothyroidism without sufficient substitution

• Hyperthyroidism

• Claustrophobia

• Smoker / habitual tobacco use

• Habitual excessive alcohol use

• Weight change of >5% within 3 months prior to inclusion

• Known or suspected non-compliance, drug or alcohol abuse

• Inability to follow the procedures of the study, e.g. due to language problems, psychological disorders, dementia, etc. of the participant

• Enrolment of the investigator, his/her family members, employees and other dependent persons

• Enrolment into another study using ionizing radiation within the previous 12 months

• Pregnant or lactating women

• Lab parameters

• Hb below lower reference limit

• Glycated Hemoglobin (HbA1c): above 6.0%

• Random plasma glucose >11 mM

Related Conditions & MeSH terms

• Brown Adipose Tissue

Intervention

Drug:
• Glyceroltrinitrat
transdermal patch

Locations

Country	Name	City	State
Switzerland	University Hospital Basel, Department of Endocrinology	Basel	BS

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Basel, Switzerland

Country where clinical trial is conducted

Switzerland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Tissue biopsies of supraclavicular BAT and skeletal muscle musculus vastus lateralis	Analysis of the transcriptional changes both in BAT and muscle which are caused by the administration of glyceroltrinitrate (Nitroderm® TTS) as compared with no intervention	After 14 days treatment with glyceroltrinitrate or after 14 days control period respectively
Primary	BAT SUVmean	18F-FDG uptake into the supra-clavicular brown adipose tissue as determined by 18F-	After 14 days treatment with glyceroltrinitrate or after 14 days control period respectively
Primary	BAT SUVmax	maximum SUV in supraclavicular adipose tissue (according to BARCIST 1.0)	After 14 days treatment with glyceroltrinitrate or after 14 days control period respectively
Secondary	BAT Volume	volume of supraclavicular adipose tissue (according to BARCIST 1.0)	After 14 days treatment with glyceroltrinitrate or after 14 days control period respectively
Secondary	BAT glycolytic volume	volume of supraclavicular adipose tissue x SUVmean (according to BARCIST 1.0)	After 14 days treatment with glyceroltrinitrate or after 14 days control period respectively
Secondary	Energy expenditure	Quantitative change in EE above resting metabolic rate in response to the respective study intervention. Measured by indirect calorimetry.	After 14 days treatment with glyceroltrinitrate or after 14 days control period respectively
Secondary	Cold induced thermogenesis	rise in energy expenditure above baseline occurring during mild cold exposure	After 14 days treatment with glyceroltrinitrate or after 14 days control period respectively
Secondary	Mixed meal test	Changes in glucose tolerance and triglyceride levels after a mixed meal test in the respective study visit.	After 14 days treatment with glyceroltrinitrate or after 14 days control period respectively
Secondary	Skin temperature	- Changes in skin temperature and body core temperature during treatment with glyceroltrinitrate (Nitroderm® TTS) compared to control.	After 14 days treatment with glyceroltrinitrate or after 14 days control period respectively