Investigation of Reboxetine, Methylphenidate Hydrochloride, and Placebo on Neurotransmitter Modulation in Exercise-Induced Fatigue in Healthy Subjects

The primary objective of this study is to **investigate the role of neurotransmitters** in fatigue. This is clinically relevant as understanding the involvement of neurotransmitters such as serotonin (5-HT), dopamine (DA), and noradrenaline (NA) in exercise-induced fatigue could lead to improved therapeutic strategies for managing fatigue-related conditions. The study aims to provide fundamental insights into the phenomenon of brain neurotransmission and its impact on fatigue, which could have significant implications for the treatment of various neurological and psychiatric disorders.

The clinical trial involves a study population consisting of **healthy** male and female individuals aged 18 to 35 years. The total number of participants is not provided as the sponsor did not give this information. Participants were selected based on specific criteria, including being non-smokers and not using any medications, with the exception of contraceptives. The trial excludes individuals with any indication of risk in general fatigue, depression, and burnout. The study does not involve a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted. The primary objective of the trial is to investigate the role of neurotransmitters in fatigue.

The clinical trial is designed to investigate the role of neurotransmitters in **fatigue**. This study employs a **randomized**, **double-blind**, and **controlled** methodology to ensure the reliability and validity of the results. Participants will be randomly assigned to receive either **reboxetine**, **methylphenidate hydrochloride**, or a **placebo**. The trial will span approximately 17 months, with an estimated recruitment start date of August 1, 2025, and an anticipated end date of December 25, 2025.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18-35 years), health status (healthy individuals), and lifestyle factors (non-smoking, no medication use except contraceptives). Following successful screening, participants will attend regular follow-up visits to monitor physiological, behavioral, and subjective changes during the onset and impact of fatigue under the influence of elevated brain neurotransmitters. The end-of-study visit will conclude the trial, where final assessments will be conducted to evaluate the primary endpoints.

The expected length of participant involvement is approximately one month, corresponding to the maximum treatment period. Conditions that may lead to early termination from the study include non-compliance with the study protocol, adverse reactions to the study medication, or withdrawal of consent by the participant. The trial is categorized as low intervention, utilizing existing pharmaceutical products to elicit neurotransmitter responses safely and acutely in healthy participants. The study does not involve any new pharmaceutical developments or therapeutic purposes, focusing solely on the scientific exploration of neurotransmitter roles in fatigue.

The clinical trial involves the administration of **Edronax** 4 mg tablets, which contain the active substance **reboxetine**. This medication is provided in tablet form and is administered orally. The maximum daily dose is 8 mg, with a total treatment period of up to one day. Reboxetine is a chemical substance, and its administration is intended to explore its effects on neurotransmitter activity related to exercise-induced fatigue and brain activation. Participant compliance with the dosing schedule will be monitored throughout the trial.

Another experimental treatment in the trial is **Rilatine Modified Release** 10 mg capsules, containing **methylphenidate hydrochloride**. These are modified-release hard capsules, also administered orally. The maximum daily dose for this medication is 20 mg, with a treatment duration of one day. Methylphenidate hydrochloride is a chemical compound, and its role in the study is to assess its impact on neurotransmitter modulation during physical exertion. Adherence to the dosing regimen will be closely observed.

The study also includes a **placebo** control, provided as **P-Tabletten** weiße 7 mm tablets. These tablets are chemically inert and are administered orally, with a maximum daily dose of 10 mg over a single day. The placebo is used to establish a baseline for comparison against the active treatments, ensuring the validity of the trial results. Participant compliance with the placebo administration will be tracked to maintain the integrity of the study data.

Efficacy in this clinical trial will be assessed through the evaluation of primary endpoints, which include physiological, behavioral, and subjective changes during the onset and impact of fatigue under the influence of elevated brain neurotransmitters. These endpoints are designed to measure the effects of neurotransmitter manipulation on exercise-induced fatigue and brain activation. The trial will utilize existing pharmaceutical products, such as **Reboxetine** and **Methylphenidate Hydrochloride**, to elicit specific neurotransmitter responses in healthy participants. The assessment of efficacy will involve monitoring changes in these parameters to determine the impact of the intervention. The trial is categorized as low intervention, as it employs safe, acutely ingested doses of existing medications without any pharmaceutical developments or therapeutic purposes. The trial is expected to conclude by December 25, 2025, with recruitment starting on August 1, 2025.