Androgen for Leydig Cell Proliferation (ALCeP)

September 21, 2018 updated by: Andrea M. Isidori, University of Roma La Sapienza

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

56

Phase

  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Italy
    • Lazio
      • Rome, Lazio, Italy, 00161
        • Dipartimento di Fisiopatologia Medica

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

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 IU (International-Unit/ml)
  • Infertility: Klinefelter Syndrome, Hypergonadotropic Hypogonadism, Hypergonadotropic Azospermia, Hypergonadotropic Cryptozoospermia
  • negative testicular tumors markers: beta-hCG (Human chorionic gonadotropin), alpha-FP (alpha-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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Nodule Size per Number
Time Frame: 4 month

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 (disappearance).
4 month

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Nodule Size
Time Frame: 4 month
Percentage change in the area of the lesion (measured with computer assisted graphics).
4 month
Luteinizing Hormone (LH)
Time Frame: 2 month
Reduction of the serum Luteinizing Hormone (LH) levels during testosterone therapy
2 month
Spermatogenesis
Time Frame: 8 month (follow-up)
Evaluation of sperm cell production after testosterone withdrawal.
8 month (follow-up)
Testicular US echo-texture
Time Frame: 36 month (follow-up)
Changes in the number of areas / nodules / lesions in the long-term safety assessment
36 month (follow-up)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2009

Primary Completion (Actual)

June 1, 2017

Study Completion (Actual)

June 1, 2018

Study Registration Dates

First Submitted

September 9, 2010

First Submitted That Met QC Criteria

September 20, 2010

First Posted (Estimate)

September 21, 2010

Study Record Updates

Last Update Posted (Actual)

September 25, 2018

Last Update Submitted That Met QC Criteria

September 21, 2018

Last Verified

September 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 160/10

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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