Androgen for Leydig Cell Proliferation (ALCeP)

This study is currently recruiting participants.
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

September 9, 2010
May 5, 2013
June 2009
October 2013   (final data collection date for primary outcome measure)
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).

Same as current
Complete list of historical versions of study NCT01206270 on ClinicalTrials.gov Archive Site
  • 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.
Same as current
Not Provided
Not Provided
 
Androgen for Leydig Cell Proliferation
Androgen Treatment in Leydig Cell Proliferation

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.

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.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Klinefelter Syndrome
  • Hypergonadotropic Hypogonadism
  • Hypergonadotropic Azospermia
  • Hypergonadotropic Cryptozoospermia
  • 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
  • Drug: Castor Oil
    4 ml of Castor Oil injected at baseline (0-week), 6-week, 18-week, 30-week.
  • Experimental: Testosterone
    Testosterone undecanoate 1000mg injection at baseline (0-week), 6-week, 18-week, 30-week
    Intervention: Drug: Testosterone undecanoate
  • Placebo Comparator: Placebo
    Injection 4 ml of castor oil at baseline (week-0), week-6, week-18, week-30
    Intervention: Drug: Castor Oil
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
20
December 2013
October 2013   (final data collection date for primary outcome measure)

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
Male
18 Years to 60 Years
No
Contact: Andrea M Isidori, MD PhD +390649970540 andrea.isidori@uniroma1.it
Contact: Daniele Gianfrilli, MD +390649970280 daniele.gianfrilli@uniroma1.it
Italy
 
NCT01206270
160/10
Yes
Andrea M. Isidori, University of Roma La Sapienza
University of Roma La Sapienza
Not Provided
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
University of Roma La Sapienza
May 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP