Primary Objective- To explore the effects of NeoRecormon on well-trained cyclists and their cycling performance by exercise parameters. Secondary Objectives- To explore the effects of NeoRecormon on well-trained cyclists and their cycling…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
Fietsprestatie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Exercise tests
All subjects will breathe during the exercise test through a facemask that will
be connected to an oxymeter to collect inspired and expired gasses for
analyzing:
- Oxygen consumption, VO2 (L/min)
- Carbon dioxide production, VCO2 (L/min)
- Respiratory minute ventilation, VE (L/min)
- Tidal volume, Vt (L)
- Respiratory frequency, Rf
- Maximal oxygen consumption, VO2,max (ml kg-1 min-1)
During the exercise tests blood will be collected at predetermined stages to
measure:
- Lactate levels
- Tissue plasminogen activator
- Creatinine phosphokinase
- C-reactive protein levels
VO2 and VCO2 will be used to calculate:
- Ventilatory equivalent for oxygen (VE/VO2), eqVO2
- Ventilatory equivalent for carbon dioxide (VE/VCO2), eqVCO2
these values will be used to determine:
- Ventilatory threshold 1, VT1
- Ventilatory threshold 2, VT2
Physiological parameters that will be determined at VT1 and VT2:
- Oxygen consumption, VO2 (L/min)
- Oxygen consumption per kg, VO2 (L/min/kg)
- Percentage of maximal oxygen consumption, %VO2max (L/min)
- Power output, P (J/s)
- Power output per kg, P (J/s/kg)
Physiological parameters that will be determined at maximal effort:
- Maximal oxygen consumption, VO2max (L/min)
- Maximal oxygen consumption per kg, VO2max (L/min/kg)
- Maximal power output, Pmax (J/s)
- Maximal power output per kg, Pmax (J/s/kg)
- Lactate values
Other determinations:
- Lactate threshold 1, LT1
- Lactate threshold 2, LT2
- Cycling economy, CE (W L-1 min-1)
- Gross efficiency, GE (%)
- Heart rate (bpm)
- Systolic blood pressure (mmHg)
- Diastolic blood pressure (mmHg)
Competition
Maximal and submaximal exercise parameters that will be measured and calculated
during the competition:
- Power (W)
- Heart rate (bpm)
- Systolic blood pressure (mmHg)
- Diastolic blood pressure (mmHg)
Secondary outcome
Safety markers:
Monitoring vital signs
o Pulse Rate (bpm)
o Systolic blood pressure (mmHg)
o Diastolic blood pressure (mmHg)
o Temperature measurements (ºC)
Electrocardiogram (ECG)
o Heart Rate (HR) (bpm), PR, QRS, QT, QTcB, QTcF
Clinical Laboratory Assessments
o Haematology
Ht must be <52%.
o Chemistry
o Urinalysis
o Coagulation (F1+2, D-Dimer, bTG, PF4, P-selectin, E-selectin,
thrombomodulin, TXB2)
Doping detection:
Detection (positive/negative test) of EPO in urine samples from subjects.
RNA expression:
RNA expression levels in venous blood before and after a submaximal exercise
test
Background summary
A recent report of the Union Cycliste Internationale gives an in-depth analysis
of doping throughout cycling*s history, from 1890 to the present day. The
report*s final conclusion is that cycling has had, and continues to have, a
serious doping problem.
Although it could be argued that administering substances that improve
performance is forbidden and nothing more needs to be known about it, research
to investigate the effects, safety and tolerability of doping substances in
this population is necessary.
There are number of reasons for this. In the first place it is often unknown if
a forbidden substance really aids performance. If this is not the case the need
for administration is strongly diminished. Additionally the adverse effects of
such substances are often insufficiently known and athletes may be exposed to
risks without being adequately informed about them.
Study objective
Primary Objective
- To explore the effects of NeoRecormon on well-trained cyclists and their
cycling performance by exercise parameters.
Secondary Objectives
- To explore the effects of NeoRecormon on well-trained cyclists and their
cycling performance by performance in a competition.
- Evaluate the safety of NeoRecormon in well-trained cyclists.
- Evaluate the performance of doping detection methods for NeoRecormon use in
well-trained cyclists.
Exploratory objectives:
- To explore how a standardized submaximal exercise affects gene expression
patterns in well-trained individuals.
- To explore the difference in RNA-profiles between individuals treated with
rHuEPO and placebo
- To identify potential transcripts that can be used as biomarkers for rHuEPO
use
- To explore correlations between changes in whole blood gene expression
patterns observed before and after a submaximal exercise test in individuals
and their performance
Study design
Randomized, double-blind, placebo-controlled study to investigate the effects
and safety of NeoRecormon in well-trained cyclists.
Intervention
Weekly subcutaneous doses of Neorecormon (5000 IU, or adjusted to reach the
desired Hemoglobin increase, maximum dose is 10.000 IU). Additionally, all
subject will receive Vitamin C and iron supplementation.
Study burden and risks
NeoRecormon is a registered drug. The safety profile of this compound is known.
Because side effects might occur and anaphylactoid reactions were observed in
isolated cases (*1/10.000) (see SmPC), the study drug administrations will be
done in the clinic under medical supervision. Subjects will be closely
monitored and will only be discharged from the unit if their medical condition
allows this.
Subjects will receive a dose of 2000, 5000 or *6000IU with a maximum of
10.000IU/week of NeoRecormon once a week for 8 weeks. The dosage depends on
haemoglobin (Hb) concentration and haematocrit (Ht) measured prior to
administration. If Ht is *52% dosage will be interrupted. If Ht is <52% the
dosage depends on the Hb concentration (see Figure 1).
The effects of NeoRecormon used in patients in an autologous blood predonation
programme most closely resembles the effects of NeoRecormon in healthy
volunteers. For the use of NeoRecormon in an autologous blood predonation
programme, the SmPC states that the maximum dose should not exceed 1200IU/kg
(or 90.000 IU for a 75kg subject) per week for subcutaneous administration.
Planned doses of 2000IU, 5000IU or *6000IU with a maximum of 10.000IU/week of
NeoRecormon will be well below this maximum dose and are therefore considered
safe. The risk is considered small and therefore acceptable compared to the
scientific benefit.
No benefit for the subjects is expected, however, their cycling performance
might be increased by EPO treatment.
Zernikedreef 8
Leiden 2333CL
NL
Zernikedreef 8
Leiden 2333CL
NL
Listed location countries
Age
Inclusion criteria
1. Well-trained (as determined by cycling history and maximal power output >4 W/kg) male subjects, 18 to 50 years old (inclusive);
2. Subjects must be healthy / medically stable on the basis of clinical laboratory tests, medical history, vital signs, and 12-lead ECG performed at screening, including exercise ECG.
3. Each subject must sign an informed consent form prior to the study. This means the subject understands the purpose of and procedures required for the study.
Exclusion criteria
1. Any clinically significant abnormality, as determined by medical history taking and physical examinations, obtained during the screening visit that in the opinion of the investigator would interfere with the study objectives or compromise subject safety.
2. Unacceptable known concomitant diagnoses or diseases at baseline, e.g., known cardiovascular, pulmonary, muscle, metabolic or haematological disease, renal or liver dysfunction, ECG or laboratory abnormalities, etc.
3. Unacceptable concomitant medications at baseline, e.g., drugs known or likely to interact with the study drugs or study assessments.
4. Unacceptable potential cycling performance enhancing medications at baseline, e.g. Erythropoiesis-stimulating agents, Anabolic Androgenic Steroids, Growth Hormone, Insulin, IGF-I and Beta-Adrenergic Agents or methods, e.g. altitude tents.
5. Blood transfusion in the past three months.
6. Loss or donation of blood over 500 mL within three months.
7. Participation in a clinical trial within 90 days of screening or more than 4 times in the previous year.
8. Known hypersensitivity to the treatment or drugs of the same class, or any of their excipients.
9. Any known factor, condition, or disease that might interfere with treatment compliance, study conduct or interpretation of the results such as drug or alcohol dependence or psychiatric disease.
10. Positive urine drug test at screening
11. Positive alcohol breath test at screening
12. Haemoglobin (Hb) concentration > 9.8 mmol/l at screening.
13. Hb concentration < 8 mmol/l at screening.
14. Haematocrit (Ht) * 48% at screening.
15. Being subject to WADA*s anti-doping rules, meaning being a member of an official cycling union or other sports union for competition (such as the KNWU) or participating in official competition during the study.
16. Positive results from serology at screening (except for vaccinated subjects or subjects with past but resolved hepatitis)
17. Previous history of fainting, collapse, syncope, orthostatic hypotension, or vasovagal reactions.
18. Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
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Other (possibly less up-to-date) registrations in this register
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In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2015-003269-27-NL |
| CCMO | NL54516.056.15 |