Effects of Micro-dose and Low-dose Recombinant Human Erythropoietin on Mitochondrial Function and Cognitive Performance

Study Overview
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Brief Summary
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A recent study by Plenge et al. revealed that rhEpo treatment enhances skeletal muscle mitochondrial respiratory capacity in humans indicating a muscle ergogenic effect of rhEpo on aerobic metabolism. The main purpose of the present study is to determine if a shorter treatment period with micro-dose as well as low-dose rhEpo has similar effects on muscle mitochondrial function. Higher doses of rhEpo is known to increase cognitive performance, but it is not clear if lower doses of rhEpo have similar effects. A second purpose of the present study is to determine if micro-dose as well as low-dose rhEpo increases cognitive performance.

Detailed Description
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Twenty-five healthy young male volunteers are randomized to either a low-dose rhEpo (60 IU/kg/week), micro-dose rhEpo (20 IU/kg/week), or placebo control (saline) group. All subjects receive two subcutaneous injections per week for four weeks. Muscle biopsies are taken at the beginning and end of the study period. Mitochondrial function is measured in permeabilized fibres using high-resolution respirometry with the substrates malate (2mM), octanoyl carnitine (1.5mM), glutamate (10mM), succinate (10mM), under saturating [ADP] (5mM), and with the membrane uncoupler FCCP (1μM). On the first day before administration of rhEpo and after the four weeks' treatment the subjects are undergoing two cognitive performance-tests, Raven Standard Progressive Matrices (Raven), and Number Finder (NUFI). Weekly semi-structured interviews are conducted by a blinded interviewer focusing on experienced change in cognitive performance.

Official Title
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Effects of Micro-dose and Low-dose Recombinant Human Erythropoietin on Mitochondrial Function and Cognitive Performance

Conditions
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Human Volunteers

Intervention / Treatment
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* Drug: Low-dose rhEpo
* Drug: Micro-dose rhEpo
* Other: Placebo Control


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Normal medical examination Weekly exercise for 0-5 hours Exclusion Criteria: Smoking daily Earlier use of performance-enhancing drugs Elite athletes Presence of cardiovascular or metabolic disease

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

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Low-dose rhEpo<br>RhEpo 60IU/kg/week | Drug: Low-dose rhEpo<br>* 60IU/kg/week<br>* Other names: Recombinant Human Erythropoitin;|
| Active Comparator: Micro-dose rhEpo<br>RhEpo 20IU/kg/week | Drug: Micro-dose rhEpo<br>* 20IU/kg/week<br>* Other names: Recombinant Human Erythropoitin;|
| Placebo Comparator: Placebo Control<br>Saline | Other: Placebo Control<br>* Saline<br>* Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximal oxygen-flux (picomol/second) |  | Four weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sum of speed-score and accuracy-score in the RAVEN-test |  | Four weeks | 
| Number of correctly found fields in the NUFI-test |  | Four weeks | 
| Rating of the interviews on a scale from -3 to +3 according to experienced change in ability to concentrate |  | Four weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Erythropoietin, Randomized controlled trial, Human volunteers, Mitochondrial function, Cognitive performance