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.
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.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
OTHER
Masking
NONE
Enrollment
60
Intramuscular injection administered for up to 25 weeks
Intramuscular injection administered for up to 25 weeks
Intramuscular injection administered for up to 25 weeks
Intramuscular injection administered for up to 25 weeks
Topical gel administered for up to 25 weeks
Intramuscular injection administered for up to 25 weeks
Intramuscular injection administered for up to 25 weeks
Topical patch administered for up to 25 weeks
Oral capsule administered for up to 25 weeks
Topical cream administered for up to 25 weeks
Oral capsule administered for up to 25 weeks
Subcutaneous injection administered for up to 25 weeks
Subcutaneous injection administered for up to 25 weeks
Oral tablet administered for up to 25 weeks
Oral tablet administered for up to 25 weeks
Oral tablet administered for up to 25 weeks
Ancillary drug: Oral tablet administered as required
Ancillary drug: Oral tablet administered as required
Ancillary drug: Oral tablet administered as required
Ancillary drug: Oral tablet administered as required
Ancillary drug: Subcutaneous injection administered as required
Ancillary drug: Subcutaneous injection administered as required
Ancillary drug: Oral tablet administered as required
Ancillary drug: Oral tablet administered as required
Ancillary drug: Oral tablet administered as required
Ancillary drug: Oral tablet administered as required
Ancillary drug: Oral tablet administered as required
Ancillary drug: Oral tablet administered as required
Ancillary drug: Oral tablet administered as required
Ancillary drug: Oral tablet administered as required
Ancillary drug: Oral tablet administered as required
Ancillary drug: Oral tablet administered as required
Ancillary drug: Oral tablet administered as required
Ancillary drug: Oral tablet administered as required
Ancillary drug: Subcutaneous injection administered as required
Ancillary drug: Oral tablet administered as required
Ancillary drug: Oral tablet administered as required
Clinical Trial Site
Abu Dhabi, United Arab Emirates
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.
Time frame: Baseline to 5.5 years.
The proportion of participants who discontinue PES due to TRAEs.
Time frame: Baseline to 5.5 years.
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)
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
Time frame: Baseline to week 27, followed by annual assessments until 5.5 years
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)
Delta in snatch and clean \& jerk (Olympic weightlifting total) measured in kilograms
Time frame: Baseline to week 27, followed by annual assessments until 5.5 years
Impact of PES on respiratory function and aerobic capacity
Change from baseline to week 27 in peak oxygen uptake (VO2 max) as measured by graded exercise test, reported in ml/kg/min.
Time frame: Baseline to week 27
Impact of PES on blood and urine markers
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).
Time frame: Baseline to 5.5 years.
Impact of PES on cardiac structure and function (a)
Change in left ventricular stroke volume (LV SV) assessed by echocardiogram. Unit: mL/m²
Time frame: Baseline to week 27, followed by annual assessments until 5.5 years
Impact of PES on cardiac structure and function (b)
Change in left ventricular ejection fraction (LVEF) and right ventricular fractional area change (RV FAC) assessed by echocardiagram. Unit: %
Time frame: Baseline to week 27, followed by annual assessments until 5.5 years.
Impact of PES on cardiac structure and function (c)
Change in left ventricular stroke volume (LV SV) and right ventricular stroke volume (RV SV) assessed by CMR imaging. Unit: mL/m²
Time frame: Baseline to week 27, followed by annual assessments until 5.5 years.
Impact of PES on cardiac structure and function (d)
Change in left ventricular ejection fraction (LVEF) and right ventricular ejection fraction (RVEF) assessed by CMR imaging. Unit: %
Time frame: Baseline to week 27, followed by annual assessments until 5.5 years.
Impact of PES on cardiac structure and function (e)
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)
Time frame: Baseline to week 27, followed by annual assessments until 5.5 years.
Impact of PES on cardiac structure and function (f)
Number of participants with abnormalities identified on resting 12-lead electrocardiography (ECG). Unit: Number of participants
Time frame: Baseline to week 27, followed by annual assessments until 5.5 years.
Impact of PES on cardiac structure and function (g)
Number of participants with abnormalities identified during exercise stress ECG. Unit: Number of participants
Time frame: Baseline to week 27, followed by annual assessments until 5.5 years.
Impact of PES on cardiac structure and function (h)
Number of participants with abnormalities identified during 24-hour ambulatory ECG monitoring. Unit: Number of participants
Time frame: Baseline to week 27, followed by annual assessments until 5.5 years.
Impact of PES on cardiac structure and function (i)
Coronary artery calcium score assessed by cardiac computed tomography (CT). Unit: Agatston score (AU), categorised as 0, 1-10, 11-100, 101-400, \>400
Time frame: Baseline with repeat imaging over 5.5 years if clinically indicated.
Impact of PES on cardiac structure and function (j)
Changes in participant qualitative description of coronary atherosclerosis assessed by cardiac computed tomography (CT). Unit: Delta in clinical abnormalities
Time frame: Baseline with repeat imaging over 5.5 years if clinically indicated.
Impact of PES on neurological function (a)
Change from baseline in cognitive memory performance (composite score of correct responses)
Time frame: Baseline to week 27
Impact of PES on neurological function (b)
Change from baseline in reaction time and processing speed. Units: milliseconds
Time frame: Baseline to week 27
Impact of PES on body composition (a)
Change from baseline in fat distribution. Unit: % of total body weight
Time frame: Baseline to week 27, followed by assessments at years 1, 3, and 5 years.
Impact of PES on body composition (b)
Change from baseline in bone mineral density at key sites (lumbar spine and hip). Unit: Z-score
Time frame: Baseline to week 27, followed by assessments at years 1, 3, and 5 years.
Impact of PES on body composition (c)
Change from baseline in landmark-based limb girth measurements (upper arm, thigh, calf) assessed by anthropometry. Unit: cm
Time frame: Baseline to week 27, followed by assessments at years 1, 3, and 5 years.
Impact of PES on body composition (d)
Change from baseline in body water distribution, including extracellular water (ECW), intracellular water (ICW), and total body water (TBW). Unit: Litres (L)
Time frame: Baseline to week 27, followed by assessments at years 1, 3, and 5 years.
Impact of PES on body composition (e)
Change from baseline in body mass index (BMI). Unit: kg/m²
Time frame: Baseline to week 27, followed by assessments at years 1, 3, and 5 years.
Impact of PES on musculoskeletal composition, function and strength (a)
Change from baseline in cross-sectional area (CSA) of hip flexors and extensors assessed by MRI. Unit: cm²
Time frame: Baseline to week 27, followed by musculoskeletal composition imaging at years 1, 3, and 5 years.
Impact of PES on musculoskeletal composition, function and strength (b)
Change from baseline in total muscle volume assessed by segmentation-based MRI analysis. Unit: cm³
Time frame: Baseline to week 27, followed by musculoskeletal composition imaging at years 1, 3, and 5 years.
Impact of PES on musculoskeletal composition, function and strength (c)
Change from baseline in muscle thickness and shape assessed by MRI. Unit: mm
Time frame: Baseline to week 27, followed by musculoskeletal composition imaging at years 1, 3, and 5 years.
Impact of PES on musculoskeletal composition, function and strength (d)
Change from baseline in grip strength. Unit: Newtons
Time frame: Baseline to week 27, followed by musculoskeletal composition imaging at years 1, 3, and 5 years.
Impact of PES on musculoskeletal composition, function and strength (e)
Incidence of musculoskeletal injuries throughout study duration. Unit: Number of events
Time frame: Baseline to week 27, followed by musculoskeletal composition imaging at years 1, 3, and 5 years.
Abdominal, adrenal and thyroid health profiling
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
Time frame: Baseline to week 27, followed by ultrasound imaging at years 1, 3, and 5 years.
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