Androgen for Leydig Cell Proliferation (ALCeP)

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by University of Roma La Sapienza
Sponsor:
Information provided by (Responsible Party):
Andrea M. Isidori, University of Roma La Sapienza
ClinicalTrials.gov Identifier:
NCT01206270
First received: September 9, 2010
Last updated: May 5, 2013
Last verified: May 2013
  Purpose

Patients with infertility often presents alterations at ultrasonographic examination of the testis. These alterations include a much higher incidence of small, multiple, non-palpable hypoechoic micro-nodules that can show internal vascularization. This finding often create alarm and anxiety, because it has to be placed in a differential diagnosis versus low-stage malignant germ cell tumors. Nevertheless, explorative surgery reveal that a consistent number of these lesion are benign, due to Leydig cell hyperplasia or Leydig cell tumours. The purpose of this study is to evaluate the effects of androgen therapy on the size and number of non-palpable hypoechoic micro-nodules in patients with elevated gonadotropin levels.


Condition Intervention Phase
Klinefelter Syndrome
Hypergonadotropic Hypogonadism
Hypergonadotropic Azospermia
Hypergonadotropic Cryptozoospermia
Drug: Testosterone undecanoate
Drug: Castor Oil
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Androgen Treatment in Leydig Cell Proliferation

Resource links provided by NLM:


Further study details as provided by University of Roma La Sapienza:

Primary Outcome Measures:
  • Nodule Size per Number [ Time Frame: 4 month ] [ Designated as safety issue: No ]

    Percentage change of the area of the lesions multiplied by the number of the measured lesions: [(area_1 + area_2 + area_3 + ... + area_n)*n].

    The latter measure account for reduction in the number of lesions (disappearence).



Secondary Outcome Measures:
  • Nodule Size [ Time Frame: 4 month ] [ Designated as safety issue: Yes ]
    Percentage change in the area of the lesion (measured with computer assisted graphics).

  • Luteinizing Hormone (LH) [ Time Frame: 2 month ] [ Designated as safety issue: No ]
    Reduction of the serum Luteinizing Hormone (LH) levels during testosterone teraphy

  • Spermatogenesis [ Time Frame: 8 month (follow-up) ] [ Designated as safety issue: Yes ]
    Evaluation of sperm cell production after testosterone withdrawl.


Estimated Enrollment: 20
Study Start Date: June 2009
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: October 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Testosterone
Testosterone undecanoate 1000mg injection at baseline (0-week), 6-week, 18-week, 30-week
Drug: Testosterone undecanoate
Testosterone undecanoate 1000mg (in 4 ml of castor oil injections) at baseline (0-week), 6-week, 18-week, 30-week
Other Name: Nebido
Placebo Comparator: Placebo
Injection 4 ml of castor oil at baseline (week-0), week-6, week-18, week-30
Drug: Castor Oil
4 ml of Castor Oil injected at baseline (0-week), 6-week, 18-week, 30-week.

Detailed Description:

Patients with the testicular dysgenesis syndrome, that comprises a variable spectrum of clinical manifestations, such as infertility, cryptorchidism, hypospadias, impaired spermatogenesis and testicular germ cell neoplasms, often develop alterations in the Leydig cell compartment. These alterations range from abnormal localization and clustering to hyperplasia or tumorous formation.

Leydig cell tumors (LCTs), although uncommon in the general population, are the most frequent non-germ cell testicular neoplasms, and their incidence has been reported increasingly growing, especially in infertile patients. Given that the focal areas of Leydig cell hyperplasia are nowadays easily detectable at ultrasonography of the testis (US), as small non-palpable hypoechoic micro-nodules that can show internal vascularization, their finding create a diagnostic challenge versus low-stage malignant germ cell tumors.

Patients with testicular dysgenesis syndrome in general exhibit an elevation of Follicle-Stimulating Hormone (FSH), but in these patients, very frequently, even Luteinizing Hormone (LH) is above the reference range. The latter can work as a growth factor for Leydig cells. Since exogenous testosterone can suppress LH levels, it could be that androgen therapy could revert the LH-induced growth stimulation of Leydig cell compartment.

The purpose of this study is to evaluate the effects of androgen therapy on the size and number of non-palpable hypoechoic micro-nodules in patients with elevated gonadotropin levels.

The purpose of this study is also to evaluate whether the behavior (UltraSonographic appearance, US) of the non-palpable hypoechoic micro-nodules during a 4-month trial of testosterone therapy can offer a novel diagnostic tool in the differential diagnosis of benign versus malignant testicular nodules.

The trial will be open only for patients with multiple non-palpable hypoechoic micro-nodules that have an elevation of both FSH and LH and that are not seeking conception.

Participants in the study will be randomized to one of two treatment groups, receiving either testosterone undecanoate (low-dose androgen) or placebo, for two 6 months. All participants will be evaluated for safety at the beginning of the study and at 2, 4, and 6 months with careful history, physical examination, blood sampling and testicular ultrasonography. Patients will also be offered the possibility to perform Magnetic Resonance Imaging (MRI) of the testis at baseline and after treatment, and/or surgical enucleation of the lesions.

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Non-palpable Multiple hypoechoic testicular nodules (with the largest having a diameter > 2 mm and < 12 mm)
  • Serum Follicle-stimulating hormone (FSH) > 7 mIU/ml (m-International-Unit/ml)
  • Serum Luteinizing hormone (LH) > 7 UI (m-International-Unit/ml)
  • Infertility: Klinefelter Syndrome, Hypergonadotropic Hypogonadism, Hypergonadotropic Azospermia, Hypergonadotropic Cryptozoospermia
  • negative testicular tumors markers: beta-hCG (Human chorionic gonadotropin), alpha-FP (Feto-Protein), CEA (Carcinoembryonic antigen), LDH (Lactate dehydrogenase), ferritin, PLAP (Placental Alkaline Phosphatase).

Exclusion Criteria:

  • Hypogonadotropic Hypogonadism
  • FSH o LH < 7 UI
  • non-homogeneous testicular lesion > 12 mm
  • positive testicular tumors markers: beta-hCG, alpha-FP, CEA, LDH, ferritin, PLAP
  • patients with contraindication to testosterone therapy: prostate cancer, PSA>4 ng/ml, severe hepatic or renal insufficiency, Hb>17, Htc>52%, severe urinary retention
  • desire to conceive
  • history of germ-cell testicular neoplasia
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01206270

Contacts
Contact: Andrea M Isidori, MD PhD +390649970540 andrea.isidori@uniroma1.it
Contact: Daniele Gianfrilli, MD +390649970280 daniele.gianfrilli@uniroma1.it

Locations
Italy
Dipartimento di Fisiopatologia Medica Recruiting
Rome, Lazio, Italy, 00161
Contact: Carlotta Pozza, MD    0649970540    carlottapozza@gmail.com   
Principal Investigator: Andrea M Isidori, MD, PhD         
Sponsors and Collaborators
University of Roma La Sapienza
Investigators
Study Chair: Andrea Lenzi, MD Sapienza University of Rome
Principal Investigator: Andrea Isidori, MD, PhD Sapienza University of Rome
Study Director: Vincenzo Bonifacio, MD, PhD Sapienza University of Rome
  More Information

No publications provided

Responsible Party: Andrea M. Isidori, Professor of Endocrinology, University of Roma La Sapienza
ClinicalTrials.gov Identifier: NCT01206270     History of Changes
Other Study ID Numbers: 160/10
Study First Received: September 9, 2010
Last Updated: May 5, 2013
Health Authority: Italy: Ethics Committee

Keywords provided by University of Roma La Sapienza:
Klinefelter
Leydig
Testicular Tumor
LH
Infertility

Additional relevant MeSH terms:
Klinefelter Syndrome
Azoospermia
Hypogonadism
Chromosome Disorders
Congenital Abnormalities
Disorders of Sex Development
Endocrine System Diseases
Genetic Diseases, Inborn
Genital Diseases, Male
Gonadal Disorders
Infertility
Infertility, Male
Sex Chromosome Disorders
Sex Chromosome Disorders of Sex Development
Urogenital Abnormalities
Androgens
Castor Oil
Methyltestosterone
Testosterone
Testosterone 17 beta-cypionate
Testosterone enanthate
Testosterone undecanoate
Anabolic Agents
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Cathartics
Gastrointestinal Agents
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions

ClinicalTrials.gov processed this record on October 21, 2014