Prevention of Sexual Offending with Cognitive Behavioral Therapy Alone Versus Therapy Combined with Testosterone Suppression – the PREVENT-MED randomized clinical trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Vaestra Goetalandsregionen

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Decision date (initial)

2026-04-24

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Swedish research council · Fredrik and Ingrid Thuring foundation · Söderström-Köngiska foundation · Region Västra götaland

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Assess the effectiveness of CBT + degarelix in reducing risk for committing sexual abuse and related behaviours in participants with psychiatric sexual disorders in comparison with CBT and placebo

Secondary objectives 13

1. Assess whether degarelix added to CBT reduces sexual offending risk and related behaviors, compared with CBT and placebo and to evaluate whether add-back treatment with minimal or low-dose testosterone is non-inferior for sexual offending risk in the secondary variable.
2. Assess whether degarelix added to CBT reduces sexual symptoms compared with CBT and placebo, and to whether add-back treatment with minimal or low-dose testosterone is non-inferior in the secondary variable.
3. Assess the extent to which degarelix added to CBT is inferior compared with CBT and placebo regarding metabolic parameters and whether add-back treatment with minimal or low-dose testosterone is superior to placebo.
4. Assess the extent to which degarelix added to CBT is inferior compared with CBT and placebo regarding adverse event profiles and whether add-back treatment with minimal or low-dose testosterone is superior to placebo.
5. Assess the extent to which degarelix added to CBT is superior compared with CBT and placebo regarding quality of life and treatment satisfaction and whether add-back treatment with minimal or low-dose testosterone is superior to placebo.
6. Assess whether the group assigned degarelix differs from placebo regarding correlation between baseline neurobiological features (e.g., cortical thickness, subcortical volumes, resting-state functional connectivity, task-based BOLD activation, pupil dilation, eye-tracking, pulse fluctuations, skin-conductance, either alone or through multimodal incorporation) and i) SOTIPS-improvement from baseline to day 365 days post randomization ii) Reduction of distress-related to pedo-/pedohebephilic disorder measured with the SSAS item 10 and 11 over the study duration.
7. Assess whether the group assigned degarelix differs from placebo regarding correlation between baseline to 4 months follow-up changes in neurobiological features (e.g., cortical thickness, subcortical volumes, resting-state functional connectivity, task-based BOLD activation, pupil dilation, eye-tracking, pulse fluctuations, skin-conductance, either alone or through multimodal incorporation) to i) SOTIPS-improvement from baseline to 121 days post randomization. ii) Scores in an off-scanner sexual responsivity paradigm (such as the Viewing Time task or questionnaires such as the HBI-19)
8. Elucidate treatment mechanisms by comparing baseline to 4 month follow-up neural changes between treatment group (degarelix versus placebo)
9. Assess whether neurobiological measures can be used to delineate disorder subtypes.
10. Sensitivity analyses that assess whether degarelix added to CBT compared with CBT and placebo differs in rate of treatment discontinuation, and whether add-back treatment with minimal or low-dose testosterone differs from placebo
11. Sensitivity analyses that assess whether degarelix added to CBT compared with CBT and placebo differs in rate of rescue interventions, and whether add-back treatment with minimal or low-dose testosterone differs from placebo.
12. Subgroup analyses of participants with pedo-/pedohebephilic disorder and other paraphilias (grouped as one) regarding efficacy in those assigned degarelix added to CBT compared with CBT and placebo in the selected variables
13. Assess the extent to which clinical characteristics interact with treatment response in the SOTIPS across the study duration in both those assigned degarelix and placebo including: i) Baseline scores in the empathic concern subscale of the Brief interpersonal reactivity index (B-IRI) ii) Baseline scores in the Ritvo Autism and Asperger diagnostic scale-revised (RAADS-14) iii) ADHD-symptoms as reported in the MINI-neuropsychiatric interview.

Conditions and MedDRA coding

Paraphilic disorder, Compulsive sexual behavior disorder

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Men age 18-70 years
2. Paraphilic disorder (6D30, 6D31, 6D32, 6D33, 6D35, 6D3Z) and/or Compulsive sexual behavior disorder (6C72)
3. Increased risk of comitting a sexual offense based on one or more of the following: I – previous conviction of sexual offense II – high risk reflected in risk rating scales (SORB/SChiMRA -A or-B >4 (range 0-10) SChiMRA+ (Part A and B): A score >4 on item #2 or #3 in SChiMRA-A, and/or at least 1 day on item #2 or #3 in SChiMRA-B. III – Investigator-rated high risk for commission of sexual offense.
4. The subject has given their written consent to participate in the trial.

Exclusion criteria 14

1. Known or suspected allergies against either product
2. Participants with mental inability, reluctance, or language difficulties that result in difficulty understanding the meaning of participation in the trial, or who are unable to speak, read, and understand Swedish or English, and respond to questions, follow instructions, complete questionnaires, and follow the study procedure, will be excluded.
3. Recent or ongoing treatments that interfere with the hypothalamic–pituitary–gonadal axis or testicular function.
4. Other diseases which, according to the investigator, can affect patient safety, treatment or trial results.
5. Not suitable for inclusion by the opinion of the investigator.
6. Known or suspected breast or prostate cancer. Clinical conditions for which there are warnings and precautions to degarelix and Tostrex
7. Diagnosed osteoporosis, or a 10-year probability of major osteoporotic fracture (MOF) is ≥15% or 10-year probability of hip fracture is ≥5% according to  Fracture Risk Assessment Tool (FRAX)(‘FRAX’, n.d.).
8. Clinically significant QT-c-prolongation >450 milliseconds Major or uncontrolled liver or kidney disease, severe asthma, or ongoing severe substance use disorder), and where the clinical risk/benefit assessment concludes a significant risk to the patient's well-being.
9. Clinically significant hepatic impairment and/or alanine aminotransferase (ALT) or aspartate aminotransferase (AST) levels exceeding four times the upper limit of normal
10. Clinically significant renal impairment and/or an estimated glomerual filtration rate <30 mL/min/1,73 m² at screening based on the revised Lund-Malmö equation (‘Njurfunktion’, n.d.).
11. Severe asthma ((≥2 exacerbations requiring systemic corticosteroids in the past 12 months or ≥1 hospitalization or emergency visit for asthma in the past year)
12. Presence of one or more major cardiovascular or metabolic risk factors, including any of the following: - known atherosclerotic disease (heart, brain, or peripheral arteries), - uncontrolled hypertension (repeated blood pressure measurements >180/110 mmHg) - type 1 or type 2 diabetes mellitus - familial hypercholesterolemia - parental history of premature myocardial or cerebral infarction (before 50 years of age)
13. Ongoing severe substance use disorder (Meets diagnostic criteria for Substance use disorder according to ICD-11 and either i] active use of illicit drugs or non-prescribed controlled substances within the past 90 days, or ii] positive urine drug screen at screening or baseline unless explained by prescribed medication).
14. Previous participation in the study.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Total score on the Sexual Offender Treatment Progress Scale (SOTIPS) score across the study duration measured at baseline, 30, 180 and 365 days post randomization.
2. Whether add-back treatment with minimal or low dose testosterone is non-inferior for risk of committing sexual abuse in the primary variable

Secondary endpoints 39

1. SOTIPS subscales sexual symptoms and antisocial opposition across the study duration
2. SOTIPS total scores at 30 days post randomization
3. SOTIPS total scores at 121 days post randomization
4. SOTIPS total scores at 244 days post randomization
5. SOTIPS total scores at 365 days post randomization
6. The SORB/SChiMRA scores across the study duration, measured at baseline and at weekly up till day 365. Self-rated, clinician-rated and proxy-rated scores will be analyzed separately.
7. The HBI-19 total scores across the study duration, measured at baseline and at 7, 14, 60, 121, 182, 244, 304, 365 days post randomization.
8. Total sexual outlet scores across the study duration, measured at baseline and at 14, 60, 121, 182, 244, 304, 365 days post randomization.
9. Total score in the Sexual symptom assessment scale, and specific scores in the distress item across the study duration, measured at baseline, pre-treatment, 7 days, 14 days, each completed iCBT module, post-treatment, booster sessions and 365 days post randomization.
10. Total score in the screening scale for sexual interests (LASSIE) measured at baseline, end of iCBT treatment and 365 days post randomization.
11. Patient desire questionnaire (PDQ) total and subscale scores (Sexual desire, satisfaction and performance, sexual activity, mood) measured at baseline and at 14, 60, 121, 182, 244, 304, 365 days post randomization.
12. Change in metabolic blood biomarkers across the study period measured at baseline and at 121, 244 and 365 days post randomization.
13. Change in bone mineral density and body fat composition on DXA-scan measured at baseline and 365 days post randomization.
14. Cumulative incidence of any AEs.
15. Cumulative incidence of severe AEs
16. Cumulative incidence of suicidal ideation requiring any type of intervention
17. Time exposure to any mild, moderate and severe adverse events respectively during the trial duration.
18. Time exposure to each adverse event reported by >5% of participants in any of four trial arms
19. Negative effects questionnaire (NEQ) scores reported at the end of iCBT-treatment.
20. Quality of life measured with the EuroQol visual analogue scale (EQ-VAS) at baseline, each iCBT module, end of iCBT treatment and at 365 days post randomization
21. Quality and frequency of treatment experiences reported at 121, 244, 365 post randomization analysed with qualitative content analysis.
22. SOTIPS-improvement from baseline to day 365 days post randomization
23. Reduction of distress-related to pedo-/pedohebephilic disorder measured with the SSAS item 10 and 11 over the study duration.
24. SOTIPS-improvement from baseline to 121 days post randomization.
25. Scores in an off-scanner sexual responsivity paradigm (such as the Viewing Time task or questionnaires such as the HBI-19)
26. Compare treatment (degarelix versus placebo) induced neural changes, primarily in task-based bold activation but possibly also structural MRI and resting-state connectivity
27. Use multimodal neurobiological (e.g., cortical thickness, subcortical volumes, resting-state functional connectivity, task-based BOLD activation, pupil dilation, eye-tracking, pulse fluctuations, skin-conductance data incorporation) possibly withmultimodal machine-learning methods, to delineate neurobiologically different phenotypes at baseline.
28. In an exploratory manner, test whether suggested disorder subtypes meaningfully predict (placebo or degarelix) treatment response over the study period.
29. Time to treatment discontinuation from injections
30. Time to treatment discontinuation from iCBT
31. Number of extra visits, sessions or contacts in addition to those specified in the protocol
32. Time to rescue medication with CPA
33. Efficacy analyses in the primary endpoint with adjustment for CPA use.
34. Time to rescue medication with tamoxifen
35. SOTIPS measured across the study duration
36. SSAS scores across the study duration (pedo-/pedohebephilic disorder)
37. Baseline scores in the empathic concern subscale of the Brief interpersonal reactivity index (B-IRI)
38. Baseline scores in the Ritvo Autism and Asperger diagnostic scale-revised (RAADS-14)
39. ADHD-symptoms as reported in the MINI-neuropsychiatric interview.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Vaestra Goetalandsregionen

Sponsor organisation

Vaestra Goetalandsregionen

Address

Regionens Hus

City

Vänersborg

Postcode

462 80

Country

Sweden

Scientific contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Valdemar Landgren

Public contact point

Organisation

Vaestra Goetalandsregionen

Contact name

Valdemar Landgren

Locations

1 EU/EEA country · 2 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 15 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications