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Rec-LH PD and Safety Profile in Hypogonadotropic Hypogonadism Men (RHYTHM)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04189133
Recruitment Status : Not yet recruiting
First Posted : December 6, 2019
Last Update Posted : July 8, 2020
Sponsor:
Information provided by (Responsible Party):
Daniele Santi, Azienda Ospedaliero-Universitaria di Modena

Brief Summary:

Objectives:

The overall clinical question is whether LH supplementation to men in indication for FSH according to the AIFA note 74, or with HH, will improve spermatogenesis and pregnancy rate (spontaneous or after ART) over FSH alone or FSH+hCG. However, since LH has never been used in men so far, the first, specific object of this study is the assessment of pharmacodynamics and safety profile of LH in HH men. To this end, this study will evaluate the pharmacodynamics and safety profile of recombinant LH (Luveris) and compare the response to Luveris and urinary hCG (Gonasi HP) in HH men. The pharmacodynamics will be assessed primarily for testosterone levels in response to increasing doses of LH and the comparison of the response to a fix dose of hCG, and later for more extend steroid profile.

Methods:

Multicentre longitudinal, interventional, randomized, open-label, phase II, clinical trial, assessing pharmacodynamics of LH in acquired HH men. The statistical hypothesis is non-inferiority of the highest LH dose employed compared to a fix hCG dose. Primary endpoint: serum testosterone levels evaluated by liquid-chromatography, tandem mass spectrometry (LC-MS/MS). Secondary endpoints: Safety and tolerability as determined by AE reporting, vital signs, and ECG, stereognosis (inhibin B, free testosterone, sex hormone binding globulin (SHBG), estradiol, whole steroid profile provided by LC-MS/MS) and testicular volume.

Patients: 32 men with acquired HH, including HH after neurosurgery for tumours or HH due to pituitary adenoma-related mass effect. Patients will be randomized (1:1) according to a permuted- blocks randomization list, to the study group, treated with Luveris (increasing doses at two weekly intervals), or to the control group treated with Gonasi HP (2000 IU twice/week). In the study group, increasing LH dosages will be administered to obtain a testosterone dose-response curve, starting with the minimum expected efficient dose (75 IU/d, sc) for two weeks followed by 150, 225 and 300 IU at two-weekly interval, respectively. The control group will be treated by the standard approach, i.e. hCG 2000 IU IM twice-weekly for 8 weeks. Patients will be further followed up for 4 weeks after treatment withdrawal. During the study, the patients will be evaluated two times per week during the treatment phase and every two weeks in the follow-up phase.


Condition or disease Intervention/treatment Phase
Acquired Hypogonadotropic Hypogonadism Drug: Lutropin alfa Drug: Human chorionic gonadotropin Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Pharmacodynamics and Safety of Human Recombinant Luteinising Hormone in Hypogonadotropic Hypogonadal Men
Estimated Study Start Date : October 1, 2020
Estimated Primary Completion Date : October 1, 2021
Estimated Study Completion Date : October 1, 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Study group
The study group will receive the daily administration sc of Luveris with increasing dosages two weeks (Treatment phase) as follows: Rec-LH 75 IU daily for 2 weeks; Rec-LH 150 IU daily for 2 weeks; Rec-LH 300 IU daily for 2 weeks; Rec-LH 600 IU daily for 2 weeks.
Drug: Lutropin alfa
daily increasing dosages of lutropin alfa
Other Name: LH

Active Comparator: Control group

The control group will receive the administration im of Gonasi HP as follows:

hCG 500 IU two times weekly, for 2 weeks; hCG 1000 IU two times weekly, for 2 weeks; hCG 1500 IU two times weekly, for 2 weeks; hCG 2000 IU two times weekly, for 2 weeks.

Drug: Human chorionic gonadotropin
human chorionic gonadotropin increasing administration
Other Name: hCG




Primary Outcome Measures :
  1. Testosterone [ Time Frame: 2 weeks after treatment start ]
    total testosterone serum levels

  2. Testosterone [ Time Frame: 4 weeks after treatment start ]
    total testosterone serum levels

  3. Testosterone [ Time Frame: 6 weeks after treatment start ]
    total testosterone serum levels

  4. Testosterone [ Time Frame: 8 weeks after treatment start ]
    total testosterone serum levels


Secondary Outcome Measures :
  1. Inhibin B [ Time Frame: 2 weeks after treatment start ]
    Inhibin B serum levels

  2. Inhibin B [ Time Frame: 4 weeks after treatment start ]
    Inhibin B serum levels

  3. Inhibin B [ Time Frame: 6 weeks after treatment start ]
    Inhibin B serum levels

  4. Inhibin B [ Time Frame: 8 weeks after treatment start ]
    Inhibin B serum levels

  5. Free testosterone [ Time Frame: 2 weeks after treatment start ]
    Free testosterone serum levels

  6. Free testosterone [ Time Frame: 4 weeks after treatment start ]
    Free testosterone serum levels

  7. Free testosterone [ Time Frame: 6 weeks after treatment start ]
    Free testosterone serum levels

  8. Free testosterone [ Time Frame: 8 weeks after treatment start ]
    Free testosterone serum levels

  9. SHBG [ Time Frame: 2 weeks after treatment start ]
    sex hormone binding globulin (SHBG)

  10. SHBG [ Time Frame: 4 weeks after treatment start ]
    sex hormone binding globulin (SHBG)

  11. SHBG [ Time Frame: 6 weeks after treatment start ]
    sex hormone binding globulin (SHBG)

  12. SHBG [ Time Frame: 8 weeks after treatment start ]
    sex hormone binding globulin (SHBG)

  13. Estradiol [ Time Frame: 2 weeks after treatment start ]
    Estradiol serum levels by LC-MS/MS evaluation

  14. Estradiol [ Time Frame: 4 weeks after treatment start ]
    Estradiol serum levels by LC-MS/MS evaluation

  15. Estradiol [ Time Frame: 6 weeks after treatment start ]
    Estradiol serum levels by LC-MS/MS evaluation

  16. Estradiol [ Time Frame: 8 weeks after treatment start ]
    Estradiol serum levels by LC-MS/MS evaluation

  17. LH [ Time Frame: 2 weeks after treatment start ]
    Serum LH

  18. LH [ Time Frame: 4 weeks after treatment start ]
    Serum LH

  19. LH [ Time Frame: 6 weeks after treatment start ]
    Serum LH

  20. LH [ Time Frame: 8 weeks after treatment start ]
    Serum LH

  21. FSH [ Time Frame: 2 weeks after treatment start ]
    Serum FSH

  22. FSH [ Time Frame: 4 weeks after treatment start ]
    Serum FSH

  23. FSH [ Time Frame: 6 weeks after treatment start ]
    Serum FSH

  24. FSH [ Time Frame: 8 weeks after treatment start ]
    Serum FSH


Other Outcome Measures:
  1. Steroids [ Time Frame: 2 weeks after treatment start ]
    Other steroids provided by the LC-MS/MS methodology

  2. Steroids [ Time Frame: 4 weeks after treatment start ]
    Other steroids provided by the LC-MS/MS methodology

  3. Steroids [ Time Frame: 6 weeks after treatment start ]
    Other steroids provided by the LC-MS/MS methodology

  4. Steroids [ Time Frame: 8 weeks after treatment start ]
    Other steroids provided by the LC-MS/MS methodology

  5. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 2 weeks after treatment start ]
    This was evaluated considering red blood cell count, marker of liver function, markers of coagulation.

  6. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 4 weeks after treatment start ]
    This was evaluated considering red blood cell count, marker of liver function, markers of coagulation.

  7. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 6 weeks after treatment start ]
    This was evaluated considering red blood cell count, marker of liver function, markers of coagulation.

  8. Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 [ Time Frame: 8 weeks after treatment start ]
    This was evaluated considering red blood cell count, marker of liver function, markers of coagulation.

  9. Testicular volume [ Time Frame: Baseline ]
    Testicular volume will be assessed locally at each visit by a physician blind to the patient group allocation

  10. Testicular volume [ Time Frame: 8 weeks after treatment start ]
    Testicular volume will be assessed locally at each visit by a physician blind to the patient group allocation



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male sex
  • Age between 18 and 45 years
  • Acquired HH forms
  • HH after neurosurgery for tumors (i.e. pituitary adenoma, including prolactinoma, craniopharyngioma, germinomas, meningiomas, gliomas, and astrocytomas). Infiltrative disease (hemochromatosis, granulomatous disease, histiocytosis, and sarcoidosis), OR
  • HH due to pituitary adenoma-related mass effect, in case of cured or controlled hormone hypersecretion
  • Total testosterone serum levels below the normal ranges (lower than 3 ng/mL)
  • No androgen replacement therapies in the last three months before enrolment
  • No hyper-secretion of other pituitary hormones

Exclusion Criteria:

HH forms, such as:

  • Combined pituitary hormone deficiency
  • Genetic syndromes (e.g., Prader-Labhart-Willi, CHARGE, Lawrence-Moon- Bardet-Biedl)
  • Iatrogenic HH forms, such as traumatic pituitary stalk interruption syndrome, irradiation, high dose corticosteroids, and anabolic steroids
  • Drug abuse and major systemic diseases
  • Chronic severe liver disease
  • Concomitant illnesses which could interfere with the study participation
  • Active malignancy diseases
  • Known or possible androgen-dependent tumors for example male breast carcinoma or prostatic carcinoma
  • Cardiac failure, hypertension, renal dysfunction, migraines, or epilepsy. (since aggravation or recurrence may occasionally be induced as a result of increased androgen production)
  • Haematocrit <40% or >54%
  • Congenital HH are excluded since these genetic forms of HH could be related to other systemic or pituitary diseases, which could bias the selection of patients.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04189133


Contacts
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Contact: Daniele Santi, MD, PhD 0593961271 daniele.santi@unimore.it
Contact: Daniele Santi 0593961271 daniele.santi@unimore.it

Locations
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Italy
Fondazione IRCCS Ca ' Grande Ospedale Maggiore Policlinico
Milan, Italy
Unit of Endocrinology of Modena
Modena, Italy, 41126
Contact: Daniele Santi    0593961271    daniele.santi@unimore.it   
Principal Investigator: Daniele Santi         
Dipartimento di Medicina Clinica e Chirurgia, Sezione di Endocrinologia, Università degli Studi di Napoli "Federico II"
Naples, Italy
Contact: Rosario Pivonello         
Sub-Investigator: Rosario Pivonello         
Department of Experimental Medicine, Section of Medical Pathophysiology, Food Science and Endocrinology, Sapienza - University of Rome
Rome, Italy
Contact: Francesco Lombardo         
Sub-Investigator: Francesco Lombardo         
ivision of Endocrinology, Diabetes and Metabolism, Department of Medical Science, University of Turin
Turin, Italy
Contact: Ezio Ghigo         
Sub-Investigator: Ezio Ghigo         
Sponsors and Collaborators
Azienda Ospedaliero-Universitaria di Modena
Publications:

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Responsible Party: Daniele Santi, Assistant Professor, Azienda Ospedaliero-Universitaria di Modena
ClinicalTrials.gov Identifier: NCT04189133    
Other Study ID Numbers: RHYTHM_20-11-2019
First Posted: December 6, 2019    Key Record Dates
Last Update Posted: July 8, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Daniele Santi, Azienda Ospedaliero-Universitaria di Modena:
luteinising hormone
male infertility
hypogonadotropic hypogonadism
human menopausal gonadotropin
Additional relevant MeSH terms:
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Hypogonadism
Gonadal Disorders
Endocrine System Diseases
Chorionic Gonadotropin
Reproductive Control Agents
Physiological Effects of Drugs