Histamine as a Molecular Transducer of Adaptation to Exercise

This study is investigating the role of histamine in generating adaptation to exercise

Study Overview

• Status: Active, not recruiting
• Conditions: Postexercise Hypotension
• Intervention / Treatment: Behavioral: Aerobic Exercise; Drug: alpha-FMH; Behavioral: Resistance and Aerobic Exercise; Drug: Antihistamine

Detailed Description

Exercise promotes and maintains healthy cardiovascular, musculoskeletal, and metabolic function, but the signals and mechanisms which transduce these effects are poorly understood. Histamine plays a role in some of the positive benefits of exercise. The goal of this study is to determine the factors that regulate exercise's effects on endothelial and vascular function, with a focus on histamine released from mast cells in skeletal muscle. Participants will perform exercise or participate in interventions like heating that may replicate some of the effects of exercise. During most experiments, investigators will insert an intravenous catheter in an arm vein and microdialysis probes in the leg, collect dialysate from the microdialysis probe and blood from the vein, record noninvasive measures, and have the participants perform exercise or undergo heating.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Oregon
    • Eugene, Oregon, United States, 97403
      • University of Oregon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Age 18 -40

Exclusion Criteria:

• Systolic ≥ 120
• Diastolic ≥ 80
• Body mass index (BMI) ˃ 28 kg/m2
• Prior diagnosis of cardiovascular disease, diabetes, autonomic disorders, or asthma
• Smoking or nicotine use
• Ongoing medical therapy (other than birth control)
• Ongoing use of over-the-counter or prescription antihistamines
• Allergies or hypersensitivities to drugs, local anesthetics, skin disinfectants, adhesives, or latex
• Pregnant, breastfeeding subjects, or planning to become pregnant in the next 12 months
• Mobility restrictions that interfere with physical activity
• High physical activity based on International Physical Activity Questionaire (IPAQ1)
• Non-English speaking

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Aerobic Exercise; Blood and skeletal muscle microdialysate collected during dynamic knee-extension exercise	Behavioral: Aerobic Exercise; Subjects will complete a single bout of aerobic exercise.
Experimental: Heating; Blood and skeletal muscle microdialysate collected during local and/or whole body heating	Drug: alpha-FMH; Subjects will undergo either local heating with diathermy or whole body heating with far-infrared sauna.; Other Names: Heating
Experimental: Resistance and Aerobic Exercise; Blood and urine collected during recovery from two modalities of exercise (This arm is now CLOSED)	Behavioral: Resistance and Aerobic Exercise; Subjects will complete bouts of resistance and aerobic exercise.
Experimental: Aerobic Exercise and Muscle Perfusion; Muscle perfusion measured during aerobic exercise (This arm is now CLOSED)	Behavioral: Aerobic Exercise; Subjects will complete a single bout of aerobic exercise.; Drug: Antihistamine; Subjects will complete a single bout of aerobic exercise under placebo vs antihistamine conditions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Histamine concentration	Histamine concentration in intramuscular dialysate	One hour
Histamine metabolites	Concentration of histamine metabolites in blood and urine	24 hours
Percentage of mast cell degranulation	Beta-hexosaminidase release from mast cells in mast cell degranulation bioassay when exposed to intramuscular dialysate from exercising individuals	One hour
Muscle perfusion	Skeletal muscle tissue oxygen index	One hour

Collaborators and Investigators

• Sponsor: University of Oregon
• Investigators: Principal Investigator: John R Halliwill, PhD, University of Oregon

Study record dates

Study Major Dates

• Study Start (Actual): July 28, 2021
• Primary Completion (Actual): December 31, 2025
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: January 11, 2022
• First Submitted That Met QC Criteria: January 11, 2022
• First Posted (Actual): January 25, 2022

Study Record Updates

• Last Update Posted (Actual): January 23, 2026
• Last Update Submitted That Met QC Criteria: January 21, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Exercise; Mast cell; Histamine
• Additional Relevant MeSH Terms: Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Primary Dysautonomias; Autonomic Nervous System Diseases; Orthostatic Intolerance; Hypotension; Behavior; Post-Exercise Hypotension; Motor Activity; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Histamine Agents; Neurotransmitter Agents; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Pharmacologic Actions; Chemical Actions and Uses; Environment and Public Health; Environment; Environment, Controlled; Histamine Antagonists; Exercise; Heating
• Other Study ID Numbers: Uoregon_STUDY0000001; STUDY00000718 (CLOSED) (Other Identifier: University of Oregon); STUDY00000982 (CLOSED) (Other Identifier: University of Oregon); STUDY00001088 (CLOSED) (Other Identifier: University of Oregon)

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