Evaluation of Metyrapone in Patients with Mild Autonomous Cortisol Secretion: A 6-Month Clinical Trial Assessing Hypertension, Glucose Metabolism, and Cortisol Levels

The primary objective of this study is to evaluate the improvement in **hypertension**, glucose metabolism, and cortisol levels in patients with mild autonomous cortisol secretion (ACS) before and after a 6-month treatment period with Metycor. This is clinically relevant as it aims to determine the efficacy of Metycor in managing key metabolic and hormonal parameters associated with ACS, potentially guiding therapeutic decisions and improving patient outcomes.

Secondary objectives include:

• Assessing improvement in other metabolic parameters such as weight, bone health, and cholesterol profile in patients with ACS before and after the treatment period.
• Evaluating the effect of the treatment on mental illness and quality of life, using disease-specific and general quality of life assessments.
• Investigating the impact of the treatment on bone health through bone density measurements and bone markers.
• Assessing changes in BMI before and after the treatment period.

The clinical trial involves participants diagnosed with **mild autonomous cortisol secretion**. The study population includes both male and female subjects, aged 18 years and older, who are not considered part of a vulnerable population. The trial aims to assess improvements in hypertension, glucose metabolism, and cortisol levels following a six-month treatment with Metycor. Participants were selected based on their diagnosis of mild autonomous cortisol secretion and the presence of one or more metabolic, bone, or psychiatric complications. Additionally, eligibility for surgical treatment with adrenalectomy was a criterion for inclusion. The sponsor has not provided information regarding the total number of participants. Lifestyle factors such as diet, physical activity, or habits were not specified as part of the selection criteria.

The clinical trial is designed to evaluate the efficacy of **metyrapone** in patients with mild autonomous cortisol secretion (ACS). This is a Phase IV, randomized, double-blind, controlled trial with an estimated duration from October 2024 to December 2025. The primary objective is to assess improvements in hypertension, glucose metabolism, and cortisol levels over a six-month treatment period. Participants will be randomly assigned to receive either the active treatment or a placebo, with neither the participants nor the investigators aware of the group assignments, ensuring a double-blind methodology.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18 years or older), presence of ACS with associated complications, and suitability for adrenalectomy. Informed consent will be obtained in accordance with ICH GCP and local regulations. The trial will include follow-up visits at baseline, three months, and six months to monitor treatment effects and safety. The end-of-study visit will occur at the conclusion of the six-month treatment period, where final assessments will be conducted.

The expected length of participant involvement is approximately six months, with conditions for early termination including adverse events, withdrawal of consent, or non-compliance with the study protocol. Primary endpoints include a reduction in s-Cortisol levels, blood pressure, and improvement in glycemic control. Secondary endpoints focus on weight reduction, changes in bone markers, LDL-cholesterol levels, quality of life, and body mass index (BMI). The trial aims to provide valuable insights into the therapeutic potential of metyrapone in managing ACS and its associated metabolic complications.

The clinical trial involves the administration of **Metycor 250 mg myke kapsler**, a pharmaceutical product containing the active substance **metyrapone**. Metycor is formulated as a **soft capsule** and is administered **orally**. The primary mechanism of action involves inhibiting an enzyme in the adrenal gland, which leads to reduced cortisol synthesis. The maximum daily dose of Metycor is 3000 mg, and the treatment period is set for a maximum of six months. The trial aims to assess improvements in hypertension, glucose metabolism, and cortisol levels in patients with autonomous cortisol secretion (ACS) before and after the treatment period.

Efficacy in the clinical trial will be assessed through a series of primary and secondary endpoints designed to evaluate the impact of Metycor on patients with autonomous cortisol secretion (ACS). The primary endpoints include the reduction of serum cortisol levels by half or to below 300 nmol/L in basal morning tests, a 10% reduction in systolic and/or diastolic blood pressure, or a 5% nocturnal dip measured via 24-hour blood pressure monitoring, and a significant improvement in glycemic control defined as a 5% reduction in HbA1C or a 10% increase in time in range (TIR). These assessments will be conducted before and after a 6-month treatment period.

Secondary endpoints will focus on additional health parameters, including a weight reduction of more than 2 kg, changes in bone markers such as PINP, CTX, and osteocalcin from degradation to build-up, a 5% decrease in LDL-cholesterol, and changes in quality of life scores measured by SF36 and the Cushing QoL questionnaire. Body Mass Index (BMI) will be measured at baseline, 3 months, and 6 months, with the effect on BMI calculated between baseline and 6 months. These efficacy parameters will be collected and analyzed using standard laboratory tests, validated scales, and patient-reported outcomes to ensure comprehensive evaluation of the treatment's impact.