Influence of Endurance Exercise and Histamine Receptors on the Gene Expression in Skeletal Muscle

Study Overview
=================
Brief Summary
-----------------
Blocking histamine H1/H2 receptors blunts chronic endurance training adaptations. The current study addresses a twofold research question: What is the influence of endurance training (1) and histamine H1 and H2 signaling (2) on the gene expression in human skeletal muscle. Results from this study will yield more insights into the molecular mechanisms of adaptations to exercise training.

Official Title
-----------------
Influence of Endurance Training and Histamine Receptor Antagonists on the Transcriptome Response in Human Muscle

Conditions
-----------------
Exercise, Histamine

Intervention / Treatment
-----------------
* Drug: Placebo: Placebo + exercise training.
* Drug: H1 blockade: H1 receptor antagonist + exercise training
* Drug: H2 Blockade: H2 receptor antagonist + exercise training


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female 18-45 years not to medium physically active Exclusion Criteria: Smoking Chronic disease Supplement or medication intake Seasonal allergies

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Randomized double-blinded placebo-controlled cross-over interventional study
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: 1: Placebo<br>lactose | Drug: Placebo: Placebo + exercise training.<br>* Oral placebo Exercise training: Interval-based cycling exercise<br>|
| Experimental: H1 blockade<br>540 mg Fexofenadine | Drug: H1 blockade: H1 receptor antagonist + exercise training<br>* H1 blockade: oral blockade Exercise training: Interval-based cycling exercise<br>|
| Experimental: H2 blockade<br>40 mg Famotidine | Drug: H2 Blockade: H2 receptor antagonist + exercise training<br>* H2 blockade: oral blockade Exercise training: Interval-based cycling exercise<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in muscle transcriptome (direct response) | RNA-sequencing | On each test-day: 0 minutes after the exercise training versus at rest. | 
| Change in muscle transcriptome (delayed response) | RNA-sequencing | On each test-day: 180 minutes after the exercise training versus at rest. | 
| Muscle glycogen depletion | Fluorometric determination of muscle glycogen levels | On each test-day: 0 minutes after the exercise training versus at rest. | 
| Muscle glycogen resynthesis | Fluorometric determination of muscle glycogen levels | On each test-day: 180 minutes after the exercise training versus at rest. | 
| Plasma volume change | Plasma volume based on hemoglobin and hematocrit concentration. | Change from rest to different time-points after exercise (0, 30, 60, 120 and 180 minutes after the exercise training). | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Heart rate during the exercise training | Heart rate during the exercise training. | Continuously during training on each test-day. | 
| Blood lactate | Capillary lactate concentration. | On each test-day at 10 time-points: at rest, during exercise and 0, 30, 60, 120 and 180 minutes after the exercise training. | 
| Blood glucose | Capillary glucose concentration. | On each test-day at 10 time-points: at rest, during exercise and 0, 30, 60, 120 and 180 minutes after the exercise training. | 
| Blood histamine | histamine concentration in blood samples. | On each test-day at 6 time-points: at rest and 0, 30, 60, 120 and 180 minutes after the exercise training. | 
| Blood insulin | insulin concentration in blood samples. | On each test-day at 6 time-points: at rest and 0, 30, 60, 120 and 180 minutes after the exercise training. | 
| Muscle signaling pathways relevant for glucose metabolism and cardiovascular health | Phosphorylation status of proteins assessed by Western Blotting | On each test-day: at rest, 0 minutes and 180 minutes after the exercise training. |