Efficacy of Degarelix Combined With Cognitive Behavioral Therapy Versus Cognitive Behavioral Therapy Alone for the Prevention of Sexual Offending in Paraphilic and Compulsive Sexual Behavior Disorders

The primary objective is to evaluate the efficacy of cognitive behavioral therapy (CBT) combined with degarelix in reducing the risk of sexual offending and related behaviors in individuals with paraphilic disorders compared to CBT plus placebo. This assessment is clinically significant for managing psychiatric sexual disorders and mitigating recidivism risk.

Secondary objectives include:

• Evaluating the impact of degarelix and testosterone add-back treatment on sexual symptoms and offending risk.
• Assessing changes in metabolic parameters and adverse event profiles.
• Measuring improvements in quality of life and treatment satisfaction.
• Investigating neurobiological features, such as cortical thickness, subcortical volumes, and resting-state functional connectivity, to elucidate treatment mechanisms and potential disorder subtypes.
• Analyzing correlations between baseline neurobiology and clinical improvements or sexual responsivity.
• Conducting sensitivity analyses on treatment discontinuation and rescue interventions.
• Performing subgroup analyses based on specific diagnoses and the influence of clinical characteristics, including empathic concern, autism, and ADHD symptoms, on treatment response.

The sponsor did not provide information regarding the total number of participants. The study population consists of men between the ages of 18 and 70 years diagnosed with a paraphilic disorder or compulsive sexual behavior disorder. Participants are characterized by an elevated risk of committing a sexual offense, determined through previous convictions, specific risk rating scales such as SORB or SChiMRA, or investigator rating. This vulnerable population is categorized as patients.

This phase 4, randomized clinical trial is designed to evaluate the effectiveness of cognitive behavioral therapy combined with degarelix compared to cognitive behavioral therapy combined with a placebo for the management of paraphilic disorder and compulsive sexual behavior disorder. The study incorporates the use of testosterone as an add-back treatment to assess its non-inferiority regarding the risk of sexual abuse. The methodology includes a screening visit to evaluate inclusion criteria, such as age, diagnosis, and specific risk ratings. Following randomization, the study involves multiple follow-up assessments at intervals including 30, 121, 180, 244, 304, and 365 days to monitor the Sexual Offender Treatment Progress Scale scores, metabolic biomarkers, and bone mineral density. The total duration of participant involvement extends to 365 days post-randomization. Early termination from the study may occur due to adverse events or discontinuation of injections or therapy.

Testosterone cipionate is administered as a 20 mg dose via cutaneous use.

Degarelix is administered via subcutaneous injection at a dosage of 2.63 mg.

The control groups receive a placebo gel identical to the testosterone gel and a placebo administered via subcutaneous injection consisting of 0.07 ml of solvents and diluting agents.

The primary efficacy assessment focuses on the total score of the Sexual Offender Treatment Progress Scale (SOTIPS) evaluated at baseline, 30, 180, and 365 days post randomization. The study evaluates whether add-back treatment with minimal or low dose testosterone is non-inferior regarding the risk of committing sexual abuse.

Secondary endpoints include various assessments of psychiatric sexual disorders and physiological changes. SOTIPS subscales for sexual symptoms and antisocial opposition, as well as total scores at specific intervals including 30, 121, 244, and 365 days post randomization, will be monitored. The SORB/SChiMRA scores, incorporating self-rated, clinician-rated, and proxy-rated measures, are assessed weekly up to day 365. The HBI-19 total scores are measured at baseline and at multiple timepoints including days 7, 14, 60, 121, 182, 244, 304, and 365. Sexual outlet scores are collected at baseline and at days 14, 60, 121, 182, 244, 304, and 365. The Sexual symptom assessment scale (SSAS) total score and specific distress items are measured at baseline, pre-treatment, 7 days, 14 days, following each cognitive behavioral therapy (CBT) module, post-treatment, during booster sessions, and at 365 days post randomization.

Additional efficacy parameters include:

• Total score of the screening scale for sexual interests (LASSIE) at baseline, end of iCBT treatment, and 365 days post randomization.
• Patient desire questionnaire (PDQ) total and subscale scores regarding sexual desire, satisfaction, performance, activity, and mood at baseline and at days 14, 60, 121, 182, 244, 304, and 365.
• Changes in metabolic blood biomarkers measured at baseline and at 121, 244, and 365 days.
• Changes in bone mineral density and body fat composition via DXA-scan at baseline and 365 days.
• Quality of life assessed using the EuroQol visual analogue scale (EQ-VAS) at baseline, each iCBT module, end of treatment, and at 365 days.
• Negative effects questionnaire (NEQ) scores at the end of iCBT treatment.

Neurobiological assessments involve comparing treatment-induced changes in BOLD activation, structural MRI, and resting-state connectivity. Exploratory measures utilize multimodal neurobiological data, such as cortical thickness, subcortical volumes, pupil dilation, eye-tracking, pulse fluctuations, and skin-conductance data, to delineate neurobiologically different phenotypes at baseline.