Thermogenesis in Hyperthyroidism and Effect of Anti-Adrenergic Therapy (HEAT)

The overall objective of the HEAT study is to determine the acute effect of propranolol on energy expenditure in patients suffering from hyperthyroidism and to evaluate the consequences of the change of hyper- to euthyroidism on metabolism during the course of treatment, especially with regard to the reaction to cold ambient temperatures.

Study Overview

• Status: Completed
• Conditions: Hyperthyroidism
• Intervention / Treatment: Drug: Propranolol

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • BS
    • Basel, BS, Switzerland, 4031
      • University Hospital Basel, Department of Endocrinology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Informed Consent as documented by signature
• Age 18 to 70 years
• Hyperthyroidism: Thyroid-stimulating Hormone (TSH) below 0.2 mU and free T4 at or above 25 pmol/L or free T3 at or above 8 pmol/L.

Exclusion Criteria:

• Contraindications to propranolol: hypersensitivity or allergy
• Therapy with a beta blocker for reasons other than hyperthyroidism (e.g. cardiac arrhythmia or heart failure)
• Treatment with amiodarone
• Women who are pregnant or breast feeding,
• Intention to become pregnant during the course of the study,
• History of asthma or chronic obstructive pulmonary disease
• Occlusive peripheral artery disease; Raynaud's syndrome.

• Other clinically significant concomitant disease states:

  • Known renal failure (GFR < 50 ml/min)
  • Known hepatic dysfunction
  • known heart failure or unstable angina pectoris
• 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,
• Participation in another study with investigational drug within the 30 days preceding and during the present study,
• Previous enrolment into the current study,
• Enrolment of the investigator, his/her family members, employees and other dependent persons.

• ECG-criteria

  • Resting heart rate below 60 bpm
  • Complete left bundle branch block
  • Atrioventricular block (AV-block) grade 2 or 3

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Propranolol 80 mg; Patients receive a single dose of 80 mg propranolol p.o.	Drug: Propranolol; Patients receive a single dose of 80 mg propranolol p.o.; Other Names: beta blockade

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
acute effect of propranolol on energy expenditure in patients suffering from hyperthyroidism	difference in resting energy expenditure (REE) measured single 90 minutes after an oral dose of 80 mg of propranolol compared to resting energy expenditure measured during the thirty minutes prior to administration of propranolol (ΔREEPropranolol).	90 minutes after propranolol application

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Respiratory quotient (RQ) before and after administration of propranolol.	Difference in respiratory quotient (RQ) before and after administration of propranolol.	90 minutes after propranolol application
Difference in skin temperature	Supraclavicular skin temperature in patients with hyperthyroidism after a single dose of 80 mg Propranolol compared to supraclavicular temperature before Propranolol.	90 minutes after propranolol application
Difference in REE from hyperthyroid to euthyroid state	indirect calorimetry to determine resting energy expenditure	after 3 to 4 months
Difference in REE hyperthyroid state to euthyroid state	indirect calorimetry to determine resting energy expenditure	after 6 to 7 months
Change in Body composition: percent body fat	dual xray absorption scan	after 3 to 4 months
Cold induced thermogenesis (CIT) in patients with hyperthyroidism	Cold induced thermogenesis: Increase in energy expenditure above resting metabolic rate in response to a mild cold stimulus during hyperthyroidism as compared to euthyroidism.	after 3 to 4 months

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland

Publications and helpful links

General Publications

• Maushart CI, Senn JR, Loeliger RC, Siegenthaler J, Bur F, Fischer JGW, Betz MJ. Resting Energy Expenditure and Cold-induced Thermogenesis in Patients With Overt Hyperthyroidism. J Clin Endocrinol Metab. 2022 Jan 18;107(2):450-461. doi: 10.1210/clinem/dgab706.

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 18, 2017
• Primary Completion (ACTUAL): February 12, 2020
• Study Completion (ACTUAL): February 12, 2020

Study Registration Dates

• First Submitted: December 7, 2017
• First Submitted That Met QC Criteria: December 14, 2017
• First Posted (ACTUAL): December 20, 2017

Study Record Updates

• Last Update Posted (ACTUAL): February 13, 2020
• Last Update Submitted That Met QC Criteria: February 12, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Hyperthyroidism; Brown adipose tissue (BAT)
• Additional Relevant MeSH Terms: Endocrine System Diseases; Thyroid Diseases; Hyperthyroidism; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Antihypertensive Agents; Vasodilator Agents; Propranolol
• Other Study ID Numbers: EKNZ 2017-02044

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No