Clinical Trials Logo

Clinical Trial Summary

This study is a continuation of two previous studies conducted at the NIH. The first study , "Treatment of True Precocious Puberty with a Long-Acting Lutenizing Hormone Releasing Hormone Analog (D-Trp(6)-Pro(9)-Net-LHRH)" had less than optimal results. Some patients, all of whom were diagnosed with familial isosexual precocious puberty, had an inadequate response to the medication and were observed to have high levels of testosterone, advanced bone aging, and other complications of the disease. As a result these patients were enrolled in a second study

In the second study, "Spironolactone Treatment for Boys with Familial Isosexual Precocious Puberty", - the patients received another medication, spironolactone (Aldactone). The drug blocked the effects of testosterone, -but bone age advancement did not improve. Some patients began experiencing gynecomastia (an abnormal growth of the male breasts). Researchers believe these may be the effects of elevated levels of estrodiol (a form of the female hormone, estrogen).

In the present study, testolactone is added to the drug regimen to block the production of estrogen. The study therefore uses spironolactone to prevent the action of the male hormones (androgen) and testolactone to block the production of female hormones (estrogen). Deslorelin, an LHRH analog which works by turning off true (central) puberty, is added to the drug regimen once true puberty begins. This is because it is know that boys with familial male precocious puberty go into true puberty too early (despite treatment with spironolactone and testolactone), and when that happens, the spironolactone and testolactone are no longer as effective. The goal of the treatment is to delay sexual development until a more appropriate age and prevent short adult stature (height).


Clinical Trial Description

Most males with precocious puberty who have been referred to NIH have been successfully treated under protocol 79-CH-0112 "Treatment of True Precocious Puberty with a Long-Acting Luteinizing Hormone Releasing Hormone Analog (D-Trp6-Pro9-Net-LHRH)." A subset of these patients, however, all of whom had familial male isosexual precocity, had an inadequate response to LHRH analog as demonstrated by high serum testosterone levels, rapid advancement in bone age, testicular growth, sperm production, and lack of regression of secondary sex characteristics. These patients had low baseline gonadotropin levels and lacked a pubertal response to LHRH, whereas the patients who had responded to LHRH analog all had clear evidence of central precocious puberty.

As an alternative approach to treatment, the patients with familial male precocious puberty were enrolled in protocol 83-CH-0028, "Spironolactone Treatment of Boys with Familial Isosexual Precocious Puberty". Spironolactone (Aldactone) is an antiandrogen that also reduced testosterone synthesis by inhibiting the enzyme 17-hydroxylase. This treatment decreased the plasma testosterone level and inhibited the peripheral effect of testosterone on target tissues. This was apparent through a decrease in acne and in the frequency of spontaneous erections.

Bone age advancement, however, was not slowed by spironolactone and gynecomastia had begun to occur in a number of patients. Both of these processes may be the result of persisting elevated estradiol levels. To attempt to reduce elevated estrogen levels in these patients to normal prepubertal levels, we plan to use testolactone (Teslac) to inhibit aromatase, the last step of estrogen biosynthesis. Testolactone has previously been used for a similar purpose in girls with gonadotropin-independent precocious puberty (McCune-Albright Syndrome) under protocol 82-CH-0165, "Testolactone treatment of girls with LHRH analog-resistant precocious puberty due to autonomous non-neoplastic ovarian estrogen secretion."

We plan to administer combined spironolactone and testolactone treatment-spironolactone to inhibit the action of androgen, and testolactone to block the formation of estrogen. The goal of this treatment is to delay sexual maturation and to prevent early closure of the epiphyses and adult short stature. These goals are being partially met with spironolactone and we postulate that the addition of testolactone will improve response by slowing bone growth and preventing gynecomastia. Preliminary results using this regimen demonstrate that blockade of both androgen action and estrogen synthesis is an effective treatment for familial male precocious puberty. Throughout the therapy, patients will receive frequent clinical, hormonal, and toxicological monitoring. ;


Study Design

Endpoint Classification: Safety/Efficacy Study, Primary Purpose: Treatment


Related Conditions & MeSH terms


NCT number NCT00001202
Study type Interventional
Source National Institutes of Health Clinical Center (CC)
Contact
Status Completed
Phase Phase 2
Start date January 1985
Completion date January 2004

See also
  Status Clinical Trial Phase
Not yet recruiting NCT01944488 - LH Response to GnRH Test in Prepubescent Girls Under 6 Years N/A
Not yet recruiting NCT01944475 - Follow-up of Girls With Premature Thelarche and Precocious Puberty N/A
Completed NCT00564850 - Efficacy and Safety Study of Pamoate of Triptorelin in Children With Precocious Puberty Phase 3
Completed NCT00001181 - Testolactone for the Treatment of Girls With LHRH Resistant Precocious Puberty Phase 2
Recruiting NCT04113070 - Overweight and Obesity and Puberty Development Cohort Study
Recruiting NCT01601171 - Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
Completed NCT00734279 - Follicle-Stimulating Hormone (FSH) and the Onset of Puberty Early Phase 1
Recruiting NCT05338411 - Effect of Exogenous Growth Hormone on Ocular Findings
Recruiting NCT06280807 - Observation of Environment and Reproductive-Endocrine Effects
Completed NCT00004344 - Purification of Testis-Stimulating Factor in Precocious Puberty N/A
Completed NCT04665713 - Effect of Prevalence of BMI on Efficacy of Herbal Medicines in Girls' Sexual Precocity
Completed NCT02199587 - The Effect of Medical Clown on the Pain and Anxiety Perception During LRH Analog Treatment or GH Provocation Test N/A
Terminated NCT04502836 - Evaluation of the Correlation Between Psychological Intervention, Including Providing Knowledge and Tools for Problems Solving, and the Anxiety Level of Female Patients Arriving to ACTH LRH Test - Pilot Study N/A
Completed NCT00006174 - Effects of Letrozole on Precocious Puberty Due to McCune Albright Syndrome Phase 1
Completed NCT02650141 - Clinical Trial of Experienced Chinese Herbal Formulas on Different Types of Precocious Puberty N/A
Completed NCT00909844 - Effects of Triptorelin Pamoate in Children With Precocious Puberty - Follow up Study Phase 3
Completed NCT00004335 - Study of Gonadotropin-Releasing Hormone Pulse Frequency in Sexual Maturation and in the Menstrual Cycle N/A