Menthol Stimulation of Brown Adipose Tissue in Humans: Aim 1

NCT07030725 | Recruiting Early Phase 1 FDA Drug

• 1 other identifier: 24695
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Brown adipose tissue becomes activated during cold conditions to increase thermogenesis (i.e., energy expenditure). Topical menthol application increases resting energy expenditure but it is unclear whether brown adipose tissue activation contributes to this rise in the energy expenditure. The overall goal with this project is to determine whether topical menthol application stimulates brown adipose tissue.

Conditions

Regulation of Energy Expenditure

Keywords

menthol; brown adipose tissue; energy expenditure

Outcome Measures

Primary Outcomes (3)

• Resting energy expenditure

  kcal/min

  from prior to the interventions to 1 hour and 2 hours post gel application

• Infrared thermography supraclavicular skin temperature

  temperature in degrees C

  from prior to the interventions to 1 hour and 2 hours post gel application

• Shivering via electromyography

  a percent of maximal activity

  from prior to the interventions to 1 hour and 2 hours post gel application

Secondary Outcomes (4)

• Body temperatures

  from prior to the interventions to 1 hour and 2 hours post gel application

• Skin blood flow

  from prior to the interventions to 1 hour and 2 hours post gel application

• Cardiovascular measurements

  from prior to the interventions to 1 hour and 2 hours post gel application

• Thermal perceptions

  from prior to the interventions to 1 hour and 2 hours post gel application

Study Arms (3)

Menthol

EXPERIMENTAL

Menthol (5% L-menthol) applied to the anterior upper body, excluding the arms, head, and neck.

Drug: Menthol Gel

Sham

SHAM COMPARATOR

A sham cream applied to the anterior upper body, excluding the arms, head, and neck.

Drug: Sham

Time control

OTHER

No cream applied to the anterior upper body.

Behavioral: Time control

Interventions

Menthol Gel DRUG

Menthol (5% L-menthol) will be applied to the anterior thorax.

Menthol

Sham DRUG

Sham gel applied to the anterior thorax.

Sham

Time control BEHAVIORAL

No gel applied to anterior thorax.

Time control

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Fluency in English
• Participate in 150 minutes or more of at least moderate intensity exercise per week during the previous year. Assessment of moderate intensity physical activity will be determined via the International Physical Activity Questionnaire (i.e., IPAQ) (described in detail in Section 7.0). This questionnaire defines moderate intensity exercise as "activities that take moderate physical effort and make you breathe somewhat harder than normal".
• Body fat ≤ 30% as determined by DEXA scan
• Be cleared for physical activity according to the 2020 Physical Activity Readiness Questionnnaire (PAR-Q+).

You may not qualify if:

• Any autonomic cardiovascular, metabolic, neurologic, endocrine, or respiratory disease, that, in the opinion of the investigator, would exclude them from participation.
• Previously diagnosed liver and/or kidney dysfunction, including, but not limited to, acute and/or chronic kidney disease, cirrhosis, hepatitis, and fatty liver disease.
• Women who are pregnant or breastfeeding.
• Current use of tobacco or electronic cigarette, or regular (i.e., more than twice a week) use within the last 1 year.
• History of peripheral cold injury, skin disorder (eczema, psoriasis), or excessive tattooing.
• Known chronic (i.e., cancer, surgery) or acute conditions (i.e., diarrhea, constipation) of the rectum.
• Menthol allergy (described in detail in Section 7.0 and 9.0). Menthol can cause skin irritation when applied topically, especially for people with sensitive skin or allergies. For this reason, recruited participants will be screened for a menthol allergy during the informed consent/screening visit. We will apply a small quantity of the cream (\~2ml) to an isolated body area to limit skin exposure. In the case a rash develops during the application of the cream, research staff will irrigate the area to remove the substance and limit further exposure. A 24-hour follow-up phone call initiated by research staff will be implemented to follow-up on all adverse reactions. Detectable BAT activation during a localized cold stress test (i.e., face cooling test) (procedure described in detail in Section 7.0).
• Using medications with direct effects on the cardiovascular system including, but not limited to:
• Anticoagulants.
• Antiplatelet agents.
• ACE Inhibitors.
• Angiotensin II receptor blockers.
• Angiotensin-receptor neprilysin inhibitors.
• Beta blockers.
• Calcium, potassium, or sodium channel blockers.

Sponsors & Collaborators

• Indiana University: lead

Study Sites (1)

Indiana University

Bloomington, Indiana, 47405, United States

RECRUITING

MeSH Terms

Interventions

salicylhydroxamic acid; Flowering time control protein FCA, Arabidopsis

Study Officials

• Blair D Johnson, PhD

  Indiana University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Felipe Pereira, MS

CONTACT

812-855-8699; hiplab@iu.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 7, 2025
• First Posted: June 22, 2025
• Study Start: March 27, 2025
• Primary Completion: March 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: June 25, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF

Locations

US (1)