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A Randomized, Double-blinded, Clinical, Placebo-controlled Trial on the Effects of Therapy With Letrozole and hUman Choriongonadotropin in Male Hypogonadism Induced by Illicit Use of Anabolic Androgenic Steroids- The LUCAS Trial

Primary Purpose

Hypogonadism, Hypogonadism, Male, Hypogonadotropic Hypogonadism

Status
Recruiting
Phase
Phase 4
Locations
Denmark
Study Type
Interventional
Intervention
Letrozole 2.5mg, hCG
Placebo
Sponsored by
Rigshospitalet, Denmark
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypogonadism

Eligibility Criteria

18 Years - 50 Years (Adult)MaleDoes not accept healthy volunteers

Inclusion Criteria:

  • • Male sex

    • 18 - 50 years of age
    • Hypogonadism following observational period of a minimum of 12 weeks since AAS discontinuation OR hypogonadism with a urine sample negative for AAS analyses at screening visit: plasma total testosterone ≤ 10 nmol/L AND featuring at least one symptom of male hypogonadism using IIEF in terms of erectile function (IIEF: Q1 - Q5 + Q15; total score < 26) and/or sexual desire (IIEF: Q11 + Q12; total < 7) (1) and/or ADAM questionnaire (YES to three questions other than question 1 and 7) and/or regular use of medical treatment for erectile dysfunction.
    • Motivation for permanent AAS cessation

Exclusion Criteria:

  • Established cardiovascular disease

    • Established diabetes of any kind 384
    • Congenital hypogonadal conditions (cryptorchidism, Klinefelter's disease, Kallmann's disease etc.)
    • Previous established hypogonadal conditions due to other causes than illicit use of AAS
    • Current or previous treatment with testosterone on other indication than AAS-induced male hypogonadism
    • Abnormal puberty development (small testes, late or absent pubic hairing, late or absent deepening of voice, etc.)
    • Current or previous pituitary diseases including pituitary tumors
    • Current or previous tumors of the hypothalamus
    • Current or former testicular cancer
    • Current or previous prostate cancer
    • Current or previous breast cancer
    • Other cancers unless complete remission ≥ 5 year
    • Other concomitant disease or makes the patient unsuitable to participate in the study
    • Severely impaired liver function
    • Allergy or hypersensitivity to the active substance (letrozole) or excipients of Letrozol "Accord"® listed in Appendix D
    • Allergy or hypersensitivity to the active substance (hCG) or excipients of Brevactid® listed in Appendix D
    • Established Lapp lactase deficiency or glucose/galactose malabsorption
    • Severe venous phlebitis or current or previous venous thromboembolism
    • Inguinal hernia
    • treatment which according to the investigators' assessment
    • Simultaneous participation in another clinical study
    • Unable to follow treatment instructions in terms of study medication instructions
    • Ongoing criminal behavior in terms of violence or illicit distribution of drugs
    • Currently or in the foreseeable future included in anti-doping programs

Sites / Locations

  • RigshospitaletRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Active Comparator

Arm Label

Active Comparator - placebo

Active comparator - treatment

Arm Description

Intervention: Intramuscular injection - placebo Intervention: Drug: placebo

Intervention: intramuscular injection - hCG Intervention: Drug: Letrozole

Outcomes

Primary Outcome Measures

Change in plasma total testosterone concentration after 24 weeks from baseline

Secondary Outcome Measures

Number of participants who adhere to AAS cessation after 24 and 50 weeks from baseline
Change in total plasma testosterone concentration after 50 weeks from baseline
Change in plasma total testosterone secretion in response to hCG stimulation after 24 and 50 weeks from baseline
Change in basal plasma pituitary gonadotropins, LH and FSH, after 24 and 50 weeks from baseline
Change in secretion of plasma pituitary gonadotropins, LH and FSH, in response to GnRH stimulation after 24 and 50 weeks from baseline
Change in sperm count after 24 and 50 weeks from baseline
Change in sperm motility after 24 and 50 weeks from baseline
Change in sperm morphology after 24 and 50 weeks from baseline
Change in sperm acrosome reaction after 24 and 50 weeks from baseline
Change in sperm DNA fragmenting after 24 and 50 weeks from baseline
Change in testicular size assessed using ultrasound after 24 and 50 weeks
Change in questionnaire score IIEF (erectile function and libido) from baseline and after 24 and 50 weeks
Change in questionnaire score ADAM (hypogonadism) from baseline and after 24 and 50 weeks
Change in questionnaire score of Major Depression Inventory (MDI) (depression) from baseline and after 24 and 50 weeks
Change in questionnaire score of (GAD7) (anxiety) from baseline and after 24 and 50 weeks
Change in questionnaire score of Buss-Perry Aggression scale (BPA) (hostility and aggression) from baseline and after 24 and 50 weeks
Change in questionnaire score of COBRA (Cognitive complaints in bipolar disorder rating assessment) from baseline and after 24 and 50 weeks
Change in questionnaire score of the Health Assessment Short Form-36 questionnaire from baseline and after 24 and 50 weeks
Change in questionnaire score of Body-Q 349 (Perception of own body) from baseline and after 24 and 50 weeks
Change in questionnaire score of the Inventory of Interpersonal Problems 32-item (IIP32) from baseline and after 24 and 50 weeks
Change in myocardial function assessed by myocardial flow reserve (mL/min/gr) by Rb-82 PET from baseline and after 24 and 50 weeks
Change in cardiac systolic function assessed using left ventricular ejection fraction (LVEF) obtained using echocardiography and 24 and 50 weeks from baseline.
Change in cardiac systolic function assessed using left ventricular global longitudinal strain (GLS) obtained using echocardiography and 24 and 50 weeks from baseline.
Change in cardiac structure (left ventricular mass) obtained using echocardiography and 24 and 50 weeks from baseline.

Full Information

First Posted
December 10, 2021
Last Updated
January 12, 2022
Sponsor
Rigshospitalet, Denmark
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1. Study Identification

Unique Protocol Identification Number
NCT05205837
Brief Title
A Randomized, Double-blinded, Clinical, Placebo-controlled Trial on the Effects of Therapy With Letrozole and hUman Choriongonadotropin in Male Hypogonadism Induced by Illicit Use of Anabolic Androgenic Steroids- The LUCAS Trial
Official Title
A Randomized, Double-blinded, Clinical, Placebo-controlled Trial on the Effects of Therapy With Letrozole and hUman Choriongonadotropin in Male Hypogonadism Induced by Illicit Use of Anabolic Androgenic Steroids on Plasma Reproductive Hormones, Fertility, Withdrawal Symptoms and Myocardial Function - The LUCAS Trial
Study Type
Interventional

2. Study Status

Record Verification Date
January 2022
Overall Recruitment Status
Recruiting
Study Start Date
November 24, 2021 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rigshospitalet, Denmark

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The overall objective of this randomized trial is to investigate the effects of treatment of AAS- induced male hypogonadism with combined therapy of letrozole and hCG compared with placebo on reproductive hormone levels, adherence to cessation of AAS use, fertility, cardiac function and quality of life.
Detailed Description
A randomized, double-blinded, clinical, placebo-controlled trial enrolling 60 male illicit AAS users with documented AAS-induced hypogonadism after a period > 12 weeks of AAS cessation or a negative urine AAS doping test. Participants will be randomized to two study groups; 24 weeks of treatment with either tablet letrozole (femar®) initial dose of 2.5 mg each day versus tablet placebo. After an initial treatment period of four weeks, intramuscular injections with either hCG, initial dose 1500 IE twice weekly (letrozole group) or isotonic saline twice weekly (placebo group) will be added to therapy if plasma total testosterone level has not increased to target plasma level. Following 24 weeks of therapy, all participants will be observed for another 26 weeks without therapy. The study will have one trial center of recruitment: Department of Endocrinology, Rigshospitalet. Following participation in the study, all participants will be offered referral to an endocrine outpatient clinic if they still display clinical and biochemical signs of male hypogonadism. A healthy group of 30 young lean eugonadal men, who have never used AAS, will be enrolled as control participants and undergo a screening visit and one visit including same procedures as the screening and randomization visits.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypogonadism, Hypogonadism, Male, Hypogonadotropic Hypogonadism

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Model Description
Allocation: Randomized Intervention Model: Parallel Assignment Masking: Double (Participant, Investigator) Primary Purpose: Treatment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active Comparator - placebo
Arm Type
Placebo Comparator
Arm Description
Intervention: Intramuscular injection - placebo Intervention: Drug: placebo
Arm Title
Active comparator - treatment
Arm Type
Active Comparator
Arm Description
Intervention: intramuscular injection - hCG Intervention: Drug: Letrozole
Intervention Type
Drug
Intervention Name(s)
Letrozole 2.5mg, hCG
Intervention Description
Drug -Treatment Intramuscular injektion - Treatment
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Drug - Placebo Intramuscular injektion - placebo
Primary Outcome Measure Information:
Title
Change in plasma total testosterone concentration after 24 weeks from baseline
Time Frame
24 weeks
Secondary Outcome Measure Information:
Title
Number of participants who adhere to AAS cessation after 24 and 50 weeks from baseline
Time Frame
24 and 50 weeks
Title
Change in total plasma testosterone concentration after 50 weeks from baseline
Time Frame
50 weeks
Title
Change in plasma total testosterone secretion in response to hCG stimulation after 24 and 50 weeks from baseline
Time Frame
24 and 50 weeks
Title
Change in basal plasma pituitary gonadotropins, LH and FSH, after 24 and 50 weeks from baseline
Time Frame
24 and 50 weeks
Title
Change in secretion of plasma pituitary gonadotropins, LH and FSH, in response to GnRH stimulation after 24 and 50 weeks from baseline
Time Frame
24 and 50 weeks
Title
Change in sperm count after 24 and 50 weeks from baseline
Time Frame
24 and 50 weeks
Title
Change in sperm motility after 24 and 50 weeks from baseline
Time Frame
24 and 50 weeks
Title
Change in sperm morphology after 24 and 50 weeks from baseline
Time Frame
24 and 50 weeks
Title
Change in sperm acrosome reaction after 24 and 50 weeks from baseline
Time Frame
24 and 50 weeks
Title
Change in sperm DNA fragmenting after 24 and 50 weeks from baseline
Time Frame
24 and 50 weeks
Title
Change in testicular size assessed using ultrasound after 24 and 50 weeks
Time Frame
24 and 50 weeks
Title
Change in questionnaire score IIEF (erectile function and libido) from baseline and after 24 and 50 weeks
Time Frame
24 and 50 weeks
Title
Change in questionnaire score ADAM (hypogonadism) from baseline and after 24 and 50 weeks
Time Frame
24 and 50 weeks
Title
Change in questionnaire score of Major Depression Inventory (MDI) (depression) from baseline and after 24 and 50 weeks
Time Frame
24 and 50 weeks
Title
Change in questionnaire score of (GAD7) (anxiety) from baseline and after 24 and 50 weeks
Time Frame
24 and 50 weeks
Title
Change in questionnaire score of Buss-Perry Aggression scale (BPA) (hostility and aggression) from baseline and after 24 and 50 weeks
Time Frame
24 and 50 weeks
Title
Change in questionnaire score of COBRA (Cognitive complaints in bipolar disorder rating assessment) from baseline and after 24 and 50 weeks
Time Frame
24 and 50 weeks
Title
Change in questionnaire score of the Health Assessment Short Form-36 questionnaire from baseline and after 24 and 50 weeks
Time Frame
24 and 50 weeks
Title
Change in questionnaire score of Body-Q 349 (Perception of own body) from baseline and after 24 and 50 weeks
Time Frame
24 and 50 weeks
Title
Change in questionnaire score of the Inventory of Interpersonal Problems 32-item (IIP32) from baseline and after 24 and 50 weeks
Time Frame
24 and 50 weeks
Title
Change in myocardial function assessed by myocardial flow reserve (mL/min/gr) by Rb-82 PET from baseline and after 24 and 50 weeks
Time Frame
24 and 50 weeks
Title
Change in cardiac systolic function assessed using left ventricular ejection fraction (LVEF) obtained using echocardiography and 24 and 50 weeks from baseline.
Time Frame
24 and 50 weeks
Title
Change in cardiac systolic function assessed using left ventricular global longitudinal strain (GLS) obtained using echocardiography and 24 and 50 weeks from baseline.
Time Frame
24 and 50 weeks
Title
Change in cardiac structure (left ventricular mass) obtained using echocardiography and 24 and 50 weeks from baseline.
Time Frame
24 and 50 weeks

10. Eligibility

Sex
Male
Gender Based
Yes
Gender Eligibility Description
Self-representation of gender identity
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: • Male sex 18 - 50 years of age Hypogonadism following observational period of a minimum of 12 weeks since AAS discontinuation OR hypogonadism with a urine sample negative for AAS analyses at screening visit: plasma total testosterone ≤ 10 nmol/L AND featuring at least one symptom of male hypogonadism using IIEF in terms of erectile function (IIEF: Q1 - Q5 + Q15; total score < 26) and/or sexual desire (IIEF: Q11 + Q12; total < 7) (1) and/or ADAM questionnaire (YES to three questions other than question 1 and 7) and/or regular use of medical treatment for erectile dysfunction. Motivation for permanent AAS cessation Exclusion Criteria: Established cardiovascular disease Established diabetes of any kind 384 Congenital hypogonadal conditions (cryptorchidism, Klinefelter's disease, Kallmann's disease etc.) Previous established hypogonadal conditions due to other causes than illicit use of AAS Current or previous treatment with testosterone on other indication than AAS-induced male hypogonadism Abnormal puberty development (small testes, late or absent pubic hairing, late or absent deepening of voice, etc.) Current or previous pituitary diseases including pituitary tumors Current or previous tumors of the hypothalamus Current or former testicular cancer Current or previous prostate cancer Current or previous breast cancer Other cancers unless complete remission ≥ 5 year Other concomitant disease or makes the patient unsuitable to participate in the study Severely impaired liver function Allergy or hypersensitivity to the active substance (letrozole) or excipients of Letrozol "Accord"® listed in Appendix D Allergy or hypersensitivity to the active substance (hCG) or excipients of Brevactid® listed in Appendix D Established Lapp lactase deficiency or glucose/galactose malabsorption Severe venous phlebitis or current or previous venous thromboembolism Inguinal hernia treatment which according to the investigators' assessment Simultaneous participation in another clinical study Unable to follow treatment instructions in terms of study medication instructions Ongoing criminal behavior in terms of violence or illicit distribution of drugs Currently or in the foreseeable future included in anti-doping programs
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Caroline Michaela Kistorp, professor, MD
Phone
+45 35 45 96 42
Email
caroline.michaela.kistorp@regionh.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Yeliz Bulut, MD
Phone
+45 35 45 80 79
Email
yeliz.bulut@regionh.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Caroline Michaela Kistorp, professor, MD
Organizational Affiliation
Rigshospitalet, Denmark
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rigshospitalet
City
Copenhagen
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caroline Michaela Kistorp, professor, MD
First Name & Middle Initial & Last Name & Degree
Yeliz Bulut, MD
Email
yeliz.bulut@regionh.dk

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

A Randomized, Double-blinded, Clinical, Placebo-controlled Trial on the Effects of Therapy With Letrozole and hUman Choriongonadotropin in Male Hypogonadism Induced by Illicit Use of Anabolic Androgenic Steroids- The LUCAS Trial

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