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Trial record 24 of 33 for:    klinefelter

Androgen for Leydig Cell Proliferation (ALCeP)

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ClinicalTrials.gov Identifier: NCT01206270
Recruitment Status : Completed
First Posted : September 21, 2010
Last Update Posted : September 25, 2018
Sponsor:
Information provided by (Responsible Party):
Andrea M. Isidori, University of Roma La Sapienza

Tracking Information
First Submitted Date  ICMJE September 9, 2010
First Posted Date  ICMJE September 21, 2010
Last Update Posted Date September 25, 2018
Study Start Date  ICMJE June 2009
Actual Primary Completion Date June 2017   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 21, 2018)
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).
Original Primary Outcome Measures  ICMJE
 (submitted: September 20, 2010)
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 (disappearence).
Change History Complete list of historical versions of study NCT01206270 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: September 21, 2018)
  • Nodule Size [ Time Frame: 4 month ]
    Percentage change in the area of the lesion (measured with computer assisted graphics).
  • Luteinizing Hormone (LH) [ Time Frame: 2 month ]
    Reduction of the serum Luteinizing Hormone (LH) levels during testosterone therapy
  • Spermatogenesis [ Time Frame: 8 month (follow-up) ]
    Evaluation of sperm cell production after testosterone withdrawal.
  • Testicular US echo-texture [ Time Frame: 36 month (follow-up) ]
    Changes in the number of areas / nodules / lesions in the long-term safety assessment
Original Secondary Outcome Measures  ICMJE
 (submitted: September 20, 2010)
  • Nodule Size [ Time Frame: 4 month ]
    Percentage change in the area of the lesion (measured with computer assisted graphics).
  • Luteinizing Hormone (LH) [ Time Frame: 2 month ]
    Reduction of the serum Luteinizing Hormone (LH) levels during testosterone teraphy
  • Spermatogenesis [ Time Frame: 8 month (follow-up) ]
    Evaluation of sperm cell production after testosterone withdrawl.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Androgen for Leydig Cell Proliferation
Official Title  ICMJE Androgen Treatment in Leydig Cell Proliferation
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Klinefelter Syndrome
  • Hypergonadotropic Hypogonadism
  • Hypergonadotropic Azospermia
  • Hypergonadotropic Cryptozoospermia
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • 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
Publications * Pozza C, Pofi R, Tenuta M, Tarsitano MG, Sbardella E, Fattorini G, Cantisani V, Lenzi A, Isidori AM, Gianfrilli D; TESTIS UNIT. Clinical presentation, management and follow-up of 83 patients with Leydig cell tumors of the testis: a prospective case-cohort study. Hum Reprod. 2019 Aug 1;34(8):1389-1403. doi: 10.1093/humrep/dez083.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 25, 2014)
56
Original Estimated Enrollment  ICMJE
 (submitted: September 20, 2010)
20
Actual Study Completion Date  ICMJE June 2018
Actual Primary Completion Date June 2017   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: Male
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Italy
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01206270
Other Study ID Numbers  ICMJE 160/10
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Andrea M. Isidori, University of Roma La Sapienza
Study Sponsor  ICMJE University of Roma La Sapienza
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account University of Roma La Sapienza
Verification Date September 2018

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