Menthol to activate brown fat in adults

Targeted TRPM8 Stimulation and Brown Adipose Tissue Activation in Humans

This trial tests whether applying menthol gel to the skin can turn on brown fat and raise energy use in healthy, active adults.

Quick facts

• Phase: Early Phase 1
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years to 40 Years
• Sex: All
• Sponsor: Indiana University (Academic / other)
• Locations: 1 site (Bloomington, Indiana)
• Trial ID: NCT07030725 on ClinicalTrials.gov

What this trial studies

Researchers will enroll healthy adults who exercise regularly and have body fat at or below 30% and randomize them to topical menthol gel, a sham application, or a time-control condition. The protocol compares changes in brown adipose tissue activity and resting energy expenditure after menthol versus control conditions. Eligibility checks include a DEXA scan for body fat and clearance for physical activity, and participants must be fluent in English. All procedures are conducted at Indiana University in Bloomington with repeated in-person visits to measure metabolic responses.

Who should consider this trial

Good fit: Ideal candidates are healthy, English-speaking adults who do at least 150 minutes per week of moderate exercise, have body fat ≤30% by DEXA, and are cleared for physical activity.

Not a fit: People with autonomic, cardiovascular, metabolic, neurologic, endocrine, respiratory diseases, known liver or kidney dysfunction, or who do not meet the activity or body-fat criteria are unlikely to benefit from participation.

Why it matters

Potential benefit: If successful, topical menthol could provide a simple, noninvasive way to boost brown fat activity and modestly increase calorie burning.

How similar studies have performed: Prior reports show topical menthol can increase resting energy expenditure, but it is unclear whether those effects are driven by brown fat activation, so this trial tests that specific mechanism.

Eligibility criteria

Inclusion Criteria:

* 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+).

Exclusion Criteria:

* 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.
  * Cholesterol lowering medications.
  * Digitalis preparations.
  * Diuretics.
  * Vasodilators.
  * Anticholinergics.

Where this trial is running

Bloomington, Indiana

• Indiana University — Bloomington, Indiana, United States (Recruiting)

Study contacts

• Principal investigator: Blair D Johnson, PhD — Indiana University
• Study coordinator: Felipe Pereira, MS

Conditions Regulation of Energy Expenditure; menthol; brown adipose tissue; energy expenditure