Clinical trial NCT03093506: Effects of Micro-dose and Low-dose Recombinant Human Erythropoietin on Mitochondrial Function and Cognitive Performance
Official title: Effects of Micro-dose and Low-dose Recombinant Human Erythropoietin on Mitochondrial Function and Cognitive Performance
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Human Volunteers
Keywords: Erythropoietin
Randomized controlled trial
Human volunteers
Mitochondrial function
Cognitive performance
Lead sponsor: Bispebjerg Hospital
Sponsor class: OTHER
First posted: 2017-03-28
Enrollment: 25
Sex: MALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Maximal oxygen-flux (picomol/second)
timeFrame: Four weeks
Secondary outcomes:
measure: Sum of speed-score and accuracy-score in the RAVEN-test
timeFrame: Four weeks
measure: Number of correctly found fields in the NUFI-test
timeFrame: Four weeks
measure: Rating of the interviews on a scale from -3 to +3 according to experienced change in ability to concentrate
timeFrame: Four weeks
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Copenhagen University Hospital Bispebjerg, Department of Anaesthesiology
state: Kbh NV
Study officials:
affiliation: Bispebjerg Hospital
name: Soeren L. Larsen
role: PRINCIPAL_INVESTIGATOR
References:
citation: Plenge U, Belhage B, Guadalupe-Grau A, Andersen PR, Lundby C, Dela F, Stride N, Pott FC, Helge JW, Boushel R. Erythropoietin treatment enhances muscle mitochondrial capacity in humans. Front Physiol. 2012 Mar 13;3:50. doi: 10.3389/fphys.2012.00050. eCollection 2012.
citation: Viuff SL, Plenge U, Belhage B, Boushel R, Koester T. Effects of low-dose recombinant human erythropoietin treatment on cognitive performance. Dan Med J. 2017 Sep;64(9):A5403.