Precocious PubertyPhase 2NCT00001202
Treatment of Boys With Precocious Puberty
A Phase 2 study testing Spironolactone, Testolactone and Deslorelin in people with Precocious Puberty, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
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. Read more about this study
- Who is it for?
- Any age, men only
- Conditions the study is for
- Precocious Puberty
- What is being tested?
- Spironolactone, Testolactone and Deslorelin
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 1985to Jan 2004
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- Men only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with familial male precocious puberty will be admitted to the Clinical Center.
- In order to be eligible for the study, the following criteria will be met:
- Boys 10 years of age or less.
- Tanner II to IV pubertal development.
- Unfused epiphyses by bone films.
- Evidence that precocious puberty is not secondary to another recognized cause of pseudopuberty:
Show all 9Show fewer
- We will exclude congenital adrenal hyperplasia, and document pretreatment androgen levels, by a 1-hour ACTH test, which will include measurement of 11-deoxycortisol and 17-OH-progesterone at 0 and 60 minutes.
- We will exclude tumor of adrenal or testes by physical exam, ultrasound, and measurement of adrenal androgens (DHA, DHAS, androstenedione).
- Elevated testosterone levels measured at 10 am, 2pm, 10 pm and 2 am over a 24 hour period.
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Child Health and Human Development (NICHD)
Bethesda, Maryland, 20892
About this study
Official title: Spironolactone and Testolactone Treatment of Boys With Familial Isosexual Precocious Puberty
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).
Read the detailed 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.
- Conditions
- Precocious Puberty
- Being tested
- Spironolactone, Testolactone, Deslorelin
- Keywords
- Luteinizing Hormone, High Serum Testosterone Levels, Low Baseline Gonadotropin, LHRH, Precocious Puberty, Familial Isosexual Precocious Puberty
- Medical subject headings
- Puberty, Precocious
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SpironolactoneDrug
TestolactoneDrug
DeslorelinDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Nov 1999 (estimated)
- Study startJan 1985
- Study completionJan 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Precocious PubertyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 80 participants
Sponsor and investigators
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00001202
- Sponsor's protocol ID
- 850016
- Other IDs
- 85-CH-0016
- Status last verified
- Jan 2004
- First submitted
- 3 Nov 1999
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Laue L, Kenigsberg D, Pescovitz OH, Hench KD, Barnes KM, Loriaux DL, Cutler GB Jr. Treatment of familial male precocious puberty with spironolactone and testolactone. N Engl J Med. 1989 Feb 23;320(8):496-502. doi: 10.1056/NEJM198902233200805.
PubMed 2492636Laue L, Jones J, Barnes KM, Cutler GB Jr. Treatment of familial male precocious puberty with spironolactone, testolactone, and deslorelin. J Clin Endocrinol Metab. 1993 Jan;76(1):151-5. doi: 10.1210/jcem.76.1.8421081.
PubMed 8421081Shenker A, Laue L, Kosugi S, Merendino JJ Jr, Minegishi T, Cutler GB Jr. A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious puberty. Nature. 1993 Oct 14;365(6447):652-4. doi: 10.1038/365652a0.
PubMed 7692306
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Spironolactone and Testolactone Treatment of Boys With Familial Isosexual Precocious Puberty
- ClinicalTrials.gov ID
- NCT00001202
- Acronym / sponsor ID
- 850016
- Conditions
- Precocious Puberty
- Keywords
- Luteinizing Hormone, High Serum Testosterone Levels, Low Baseline Gonadotropin, LHRH, Precocious Puberty, Familial Isosexual Precocious Puberty
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants
- Lead sponsor
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)US National Institutes of Health
- Study start
- Jan 1985
- Study completion
- Jan 2004
- First posted
- 4 Nov 1999 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed 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
- Primary purpose
- Treatment
Who may qualify
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (9 listed)
- Patients with familial male precocious puberty will be admitted to the Clinical Center.
- Boys 10 years of age or less.
- Tanner II to IV pubertal development.
- Unfused epiphyses by bone films.
- Evidence that precocious puberty is not secondary to another recognized cause of pseudopuberty:
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Spironolactone | Drug | – |
| Testolactone | Drug | – |
| Deslorelin | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 2492636Laue L, Kenigsberg D, Pescovitz OH, Hench KD, Barnes KM, Loriaux DL, Cutler GB Jr. Treatment of familial male precocious puberty with spironolactone and testolactone. N Engl J Med. 1989 Feb 23;320(8):496-502. doi: 10.1056/NEJM198902233200805.
- Background: PubMed 8421081Laue L, Jones J, Barnes KM, Cutler GB Jr. Treatment of familial male precocious puberty with spironolactone, testolactone, and deslorelin. J Clin Endocrinol Metab. 1993 Jan;76(1):151-5. doi: 10.1210/jcem.76.1.8421081.
- Background: PubMed 7692306Shenker A, Laue L, Kosugi S, Merendino JJ Jr, Minegishi T, Cutler GB Jr. A constitutively activating mutation of the luteinizing hormone receptor in familial male precocious puberty. Nature. 1993 Oct 14;365(6447):652-4. doi: 10.1038/365652a0.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Spironolactone, Testolactone and Deslorelin in people with Precocious Puberty, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00001202, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Mar 2008.