Safety and Impact of Medically Supervised Performance Enhancing Substance Usage in Healthy Elite Athletes
Conditions
Brief summary
Objectives: The primary objective is to assess the safety and tolerability of medical drugs with the potential to enhance performance (PES) in professional athletes over a 5.5 year period, encompassing a 25-week PES Exposure period and 5 year long term follow-up of period comprehensive health and safety monitoring. The secondary objective is to evaluate the impact of PES on athletic performance through validated sport specific and clinical assessments. Methods: This prospective hybrid design study will enrol 60 adult participants, divided into two groups. The first group will receive performance-enhancing substances (PES) directly through the study, administered as Investigational Medicinal Products (IMPs) under comprehensive medical supervision for up to 25 weeks. The second group will include natural athletes and those already using PES prescribed by their own doctors. All substances used in this study are medically approved by national regulatory agencies (e.g., FDA, MHRA, EMA, EDE, etc.), and market authorised. Participants undergo enrollment and baseline health and performance assessments, prior to a 25 weeks of PES exposure. During the period of PES exposure, participants undergo periodic monitoring of comprehensive physiological biomarkers alongside subjective assessments. Following the PES exposure phase, participants will complete repeat baseline health and performance assessments, followed by a titration phase and, where indicated, post-cycle therapy (PCT) to support the restoration of physiological function toward baseline. The study will conclude with a five-year longitudinal follow-up period to monitor long-term health outcomes. During this phase, participants will undergo annual assessments, including cardiac electrocardiography (ECG), echocardiography, magnetic resonance imaging (MRI), blood and urine biomarkers, routine vital signs, and quality-of-life measures. Additional imaging will include brain functional MRI (fMRI) and vital organ ultrasound at years 1, 3, and 5, with cardiac CT performed as clinically indicated. Athlete safety biomarker assessments, clinical evaluations, and adverse event reporting, will be continuously evaluated by study doctors and with additional safety oversight from a Data Safety Monitoring Board, Independent Medical Commission (a multidisciplinary panel of medical experts), and a Medical Monitor.
Detailed description
This study employs a prospective hybrid design comprising an observational cohort alongside a non-randomised interventional cohort, allowing for individualized PES regimens, biomarker-informed adaptation, and alignment with each athlete's training cycle while providing for the first time prospective data on safety parameters and performance effects of PES. It emphasizes within-subject change over time rather than between-group comparisons, offering a more ecologically valid framework for observing enhancement in context. Participants will continue periodized training while under continuous monitoring, enabling assessment of both physiological response and performance progression under real-world conditions. Similar study designs that aim to determine optimal therapy customization to individuals with specific biomarkers are becoming increasingly popular in precision medicine.
Interventions
DRUGTestosterone Enanthate
Intramuscular injection administered for up to 25 weeks
DRUGTestosterone Cypionate
Intramuscular injection administered for up to 25 weeks
Intramuscular injection administered for up to 25 weeks
Intramuscular injection administered for up to 25 weeks
DRUGTestosterone Gel
Topical gel administered for up to 25 weeks
DRUGMethenolone Enanthate (Primobolan)
Intramuscular injection administered for up to 25 weeks
DRUGNandrolone Decanoate (Deca-Durabolin)
Intramuscular injection administered for up to 25 weeks
DRUGEstradiol Patch
Topical patch administered for up to 25 weeks
DRUGEstradiol Capsule
Oral capsule administered for up to 25 weeks
DRUGProgesterone Cream
Topical cream administered for up to 25 weeks
Oral capsule administered for up to 25 weeks
DRUGHuman Growth Hormone (hGH)
Subcutaneous injection administered for up to 25 weeks
DRUGEPO Darbepoetin (Aranesp)
Subcutaneous injection administered for up to 25 weeks
DRUGMeldonium
Oral tablet administered for up to 25 weeks
DRUGModafinil
Oral tablet administered for up to 25 weeks
DRUGMixed amphetamine salts (Adderall)
Oral tablet administered for up to 25 weeks
DRUGClomiphene
Ancillary drug: Oral tablet administered as required
DRUGAnastrozole
Ancillary drug: Oral tablet administered as required
DRUGLevothyroxine
Ancillary drug: Oral tablet administered as required
DRUGLiothyronine
Ancillary drug: Oral tablet administered as required
DRUGhCG
Ancillary drug: Subcutaneous injection administered as required
DRUGhMG
Ancillary drug: Subcutaneous injection administered as required
DRUGAtorvastatin
Ancillary drug: Oral tablet administered as required
DRUGRosuvastatin
Ancillary drug: Oral tablet administered as required
DRUGBisoprolol
Ancillary drug: Oral tablet administered as required
DRUGNebivolol
Ancillary drug: Oral tablet administered as required
DRUGMetoprolol
Ancillary drug: Oral tablet administered as required
DRUGPropranolol
Ancillary drug: Oral tablet administered as required
DRUGLisinopril
Ancillary drug: Oral tablet administered as required
DRUGEnalapril
Ancillary drug: Oral tablet administered as required
DRUGFurosemide
Ancillary drug: Oral tablet administered as required
DRUGChlorothiazide
Ancillary drug: Oral tablet administered as required
DRUGCabergoline
Ancillary drug: Oral tablet administered as required
DRUGMetformin
Ancillary drug: Oral tablet administered as required
DRUGBasal Insulin Glargine (long-acting)
Ancillary drug: Subcutaneous injection administered as required
DRUGTelmisartan
Ancillary drug: Oral tablet administered as required
DRUGLosartan
Ancillary drug: Oral tablet administered as required
Sponsors
Enhanced Emirates Limited
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Participants are eligible to be included in the study only if all the following criteria apply: 1. Participant must be 18 years of age or older at the time of signing the informed consent. 2. Capable of giving signed informed consent, which includes compliance with the requirements and restrictions listed in the ICF and in this protocol. 3. For a participant that intends to and uses PES as part of the study, the participant must be retired from professional sporting organizations that prohibit the performance enhancing substances and substances studied and must not be subject to active anti-doping regulations or testing pools at the time of enrollment. 4. Participant must be under the care of a primary care provider (PCP). 5. Participant passes medical profiling assessment (measuring overall state of health and quality of life) 6. Females must meet one of the following: 1. Postmenopausal (\>45 years of age with amenorrhea for at least 12 months, without using exogenous hormonal contraception and with FSH ≥ 40 IU/L). 2. Surgically sterile (hysterectomy, bilateral salpingectomy; oophorectomy) for at least 6 months. 3. Using a double contraception including a barrier method (condom, diaphragm, or occlusive cap) and a highly effective method of birth control, which includes the following: i. Established use (i.e. at least 90 days prior to signing of ICF) of combined (estrogen and progestogen) oral, intravaginal, or transdermal hormonal contraceptive associated with inhibition of ovulation. ii. Established use (i.e. at least 90 days prior to signing of ICF) of progestogen- only oral, injectable, or implantable hormonal contraceptive associated with inhibition of ovulation. iii. Established use (i.e. at least 90 days prior to signing of ICF) of an intrauterine device (IUD) or intrauterine hormone-releasing system (IUS). iv. Bilateral tubal occlusion completed at least 90 days prior to signing of ICF. d) Vasectomized partner with the appropriate post-vasectomy documentation of the absence of spermatozoa in the ejaculate. Participant must provide documentation before the first dose of PES. e) Sexual abstinence, when this is in line with the preferred and usual lifestyle of the participant.
Exclusion criteria
Participants are excluded from the study if any of the following criteria apply: 1. A self-reported history of any significant psychological or psychiatric challenges that may affect their ability to safely engage in the study or comply with study procedures. This includes, but is not limited to: 1. Ongoing or recently unstable conditions such as severe depression or other psychiatric disorders that have not been effectively managed, in the judgement of the clinical research team. 2. A history of severe mental health conditions (e.g., schizophrenia, bipolar disorder) that have required intensive intervention or hospitalization within the past 5 years. 2. Prior history of malignancy (including breast cancer, lymphoma, leukemia) within the past 5 years except for cervical or prostate carcinoma in situ that has been completely resected or cured basal or squamous cell skin carcinoma. 3. Has a history of CV disease that includes any of the following: 1. Unstable CV disease, myocardial infarction, unstable angina, cardiac bypass or coronary arteries stenting, cerebrovascular accident (stroke), or transient ischemic attack. 2. Clinically significant cardiac arrhythmias, including congenital arrhythmia syndromes (e.g. Long QT syndrome, Brugada Syndrome) or acquired arrhythmias, including pacemaker or ICD. Note. Cases will be considered on a case-by-case basis following an expert sports cardiology review using the newest internationally published recommendations. 3. Congestive heart failure (New York Heart Association class II to IV symptoms) or inherited or acquired cardiomyopathies Note. Cases will be considered on a case-by-case basis following an expert sports cardiology review using the newest internationally published recommendations. 4. Current or history of clinically significant (per Investigator's judgment) liver or biliary disease. 5. Current acute or chronic self-reported HCV and/or HBV infection. 6. Current or history of clinically significant renal disease (per Investigator's judgment) or GFR \<60mL/min/1.73m2 7. Has history or presence of any results from Screening Visit laboratory tests, ECG, physical examination, or vital signs that, in the opinion of the Investigator, Medical Monitor, or Sponsor, should be exclusionary for such a candidate. 8. The use of other investigational drugs at the time of screening or within 30 days or 5 half- lives prior to signing of the ICF, whichever is longer, or longer if required by local regulations. Note. Upon entry into the long-term follow-up phase of the study, participation in another clinical trial may be permitted only if it does not interfere with the objectives of this study. This is at the discretion of the study Investigator. 9. Pregnant or breastfeeding. 10. Has a mental or legal incapacity. 11. Is unwilling to provide written informed consent or is unable to follow the procedures outlined in the Protocol. Prospective approval of protocol deviations to recruitment and eligibility criteria, also known as protocol waivers or exemptions, is not permitted.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The proportion of participants who discontinue PES due to TRAEs. | Baseline to 5.5 years. |
| The incidence and severity of Treatment-related adverse events (TRAEs), including adverse events (AEs) and serious adverse events (SAEs), as assessed by the study physicians from baseline to 5.5 years after enrollment. | Baseline to 5.5 years. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Impact of PES on cardiac structure and function (b) | Baseline to week 27, followed by annual assessments until 5.5 years. | Change in left ventricular ejection fraction (LVEF) and right ventricular fractional area change (RV FAC) assessed by echocardiagram. Unit: % |
| Impact of PES on cardiac structure and function (c) | Baseline to week 27, followed by annual assessments until 5.5 years. | Change in left ventricular stroke volume (LV SV) and right ventricular stroke volume (RV SV) assessed by CMR imaging. Unit: mL/m² |
| Impact of PES on cardiac structure and function (d) | Baseline to week 27, followed by annual assessments until 5.5 years. | Change in left ventricular ejection fraction (LVEF) and right ventricular ejection fraction (RVEF) assessed by CMR imaging. Unit: % |
| Impact of PES on cardiac structure and function (e) | Baseline to week 27, followed by annual assessments until 5.5 years. | Qualitative assessment of left and right ventricular myocardial fibrosis by location and extent using late gadolinium enhancement (LGE) on CMR imaging. Unit: Qualitative description (location and extent of fibrosis) |
| Impact of PES on cardiac structure and function (f) | Baseline to week 27, followed by annual assessments until 5.5 years. | Number of participants with abnormalities identified on resting 12-lead electrocardiography (ECG). Unit: Number of participants |
| Impact of PES on cardiac structure and function (g) | Baseline to week 27, followed by annual assessments until 5.5 years. | Number of participants with abnormalities identified during exercise stress ECG. Unit: Number of participants |
| Impact of PES on cardiac structure and function (h) | Baseline to week 27, followed by annual assessments until 5.5 years. | Number of participants with abnormalities identified during 24-hour ambulatory ECG monitoring. Unit: Number of participants |
| Impact of PES on cardiac structure and function (i) | Baseline with repeat imaging over 5.5 years if clinically indicated. | Coronary artery calcium score assessed by cardiac computed tomography (CT). Unit: Agatston score (AU), categorised as 0, 1-10, 11-100, 101-400, \>400 |
| Impact of PES on cardiac structure and function (j) | Baseline with repeat imaging over 5.5 years if clinically indicated. | Changes in participant qualitative description of coronary atherosclerosis assessed by cardiac computed tomography (CT). Unit: Delta in clinical abnormalities |
| Impact of PES on neurological function (a) | Baseline to week 27 | Change from baseline in cognitive memory performance (composite score of correct responses) |
| Impact of PES on neurological function (b) | Baseline to week 27 | Change from baseline in reaction time and processing speed. Units: milliseconds |
| Impact of PES on body composition (a) | Baseline to week 27, followed by assessments at years 1, 3, and 5 years. | Change from baseline in fat distribution. Unit: % of total body weight |
| Impact of PES on body composition (b) | Baseline to week 27, followed by assessments at years 1, 3, and 5 years. | Change from baseline in bone mineral density at key sites (lumbar spine and hip). Unit: Z-score |
| Impact of PES on body composition (c) | Baseline to week 27, followed by assessments at years 1, 3, and 5 years. | Change from baseline in landmark-based limb girth measurements (upper arm, thigh, calf) assessed by anthropometry. Unit: cm |
| Impact of PES on body composition (d) | Baseline to week 27, followed by assessments at years 1, 3, and 5 years. | Change from baseline in body water distribution, including extracellular water (ECW), intracellular water (ICW), and total body water (TBW). Unit: Litres (L) |
| Impact of PES on body composition (e) | Baseline to week 27, followed by assessments at years 1, 3, and 5 years. | Change from baseline in body mass index (BMI). Unit: kg/m² |
| Impact of PES on musculoskeletal composition, function and strength (a) | Baseline to week 27, followed by musculoskeletal composition imaging at years 1, 3, and 5 years. | Change from baseline in cross-sectional area (CSA) of hip flexors and extensors assessed by MRI. Unit: cm² |
| Impact of PES on musculoskeletal composition, function and strength (b) | Baseline to week 27, followed by musculoskeletal composition imaging at years 1, 3, and 5 years. | Change from baseline in total muscle volume assessed by segmentation-based MRI analysis. Unit: cm³ |
| Impact of PES on musculoskeletal composition, function and strength (c) | Baseline to week 27, followed by musculoskeletal composition imaging at years 1, 3, and 5 years. | Change from baseline in muscle thickness and shape assessed by MRI. Unit: mm |
| Impact of PES on musculoskeletal composition, function and strength (d) | Baseline to week 27, followed by musculoskeletal composition imaging at years 1, 3, and 5 years. | Change from baseline in grip strength. Unit: Newtons |
| Impact of PES on musculoskeletal composition, function and strength (e) | Baseline to week 27, followed by musculoskeletal composition imaging at years 1, 3, and 5 years. | Incidence of musculoskeletal injuries throughout study duration. Unit: Number of events |
| Abdominal, adrenal and thyroid health profiling | Baseline to week 27, followed by ultrasound imaging at years 1, 3, and 5 years. | Number of participants with abnormal clinical findings on abdominal, adrenal, and thyroid imaging (ultrasound), including abnormalities of organ size and structure (liver, kidneys, pancreas, spleen, gallbladder, bile ducts, adrenal glands, thyroid glands), tears, hernias, and pathological findings such as tumours, nodules, cysts, aneurysms, thrombosis, or inflammation. Unit: Number of participants |
| Changes in sport-specific performance metrics, tailored to the athlete's discipline, in order to assess how individualized PES regimens translate into functional outcomes relevant to each sport (a) | Baseline to week 27, followed by annual assessments until 5.5 years | Delta in 100-meter track sprint time, 50-meter freestyle swim time, 100-meter freestyle swim time, 50-meter butterfly swim time, and 100-meter butterfly swim time, measured in seconds |
| Changes in sport-specific performance metrics, tailored to the athlete's discipline, in order to assess how individualized PES regimens translate into functional outcomes relevant to each sport (b) | Baseline to week 27, followed by annual assessments until 5.5 years | Delta in snatch and clean \& jerk (Olympic weightlifting total) measured in kilograms |
| Impact of PES on blood and urine markers | Baseline to 5.5 years. | Number of participants with abnormal laboratory tests results. Measured from baseline through 5.5 years comprising up to 25 week PES exposure followed by a 5-year annual longitudinal follow-up. Markers include oxygen transport and immune system balance (CBC with 5-part differential); organ function and metabolic stress (comprehensive metabolic panel); iron status and oxygen-carrying capacity (serum iron, ferritin, transferrin saturation, TIBC); cardiovascular health and lipid metabolism (HDL, LDL, VLDL, triglycerides, Apo A1/B, lipoprotein(a)); hormonal balance and endocrine resilience (testosterone, estrogen, cortisol, DHEA, TSH, T3, T4, LH, FSH, prolactin); electrolyte and hydration balance (sodium, potassium, calcium, magnesium, chloride); systemic inflammation and immune activation (hs-CRP, ferritin, alpha-1 antitrypsin); and fatty acid profile and cellular membrane health (omega-3/omega-6 balance, EPA/DHA ratio, arachidonic acid). |
| Impact of PES on respiratory function and aerobic capacity | Baseline to week 27 | Change from baseline to week 27 in peak oxygen uptake (VO2 max) as measured by graded exercise test, reported in ml/kg/min. |
| Impact of PES on cardiac structure and function (a) | Baseline to week 27, followed by annual assessments until 5.5 years | Change in left ventricular stroke volume (LV SV) assessed by echocardiogram. Unit: mL/m² |
Countries
United Arab Emirates
Outcome results
None listed