Kisspeptin in the Evaluation of Delayed Puberty

Study Overview
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Brief Summary
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The goal of this study is to test whether the hormone kisspeptin has the potential to prospectively diagnose adolescents with self-resolving or permanent delayed puberty. Some children with delayed puberty will eventually enter puberty on their own. However, some children with delayed puberty have a permanent condition and require medical treatment to undergo puberty. Right now, there is no reliable diagnostic tool to tell whether a child's delayed puberty will be self-resolving or permanent. The hormone kisspeptin has the potential to prospectively diagnose adolescents with self-resolving or permanent delayed puberty.

Detailed Description
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The investigators are seeking boys (ages 13.5-17 years) and girls (ages 12-17) years with a diagnosis of delayed puberty. Study participation involves 2 outpatient visits and two hospital admissions (one 11-hour, overnight admission and one 6-hour day admission) when subjects will receive two investigational drugs, the naturally occurring hormones kisspeptin and gonadotropin-releasing hormone (GnRH). Subjects will then be followed every 6 months until they reach 18 years of age to determine if their pubertal delay was self-resolved or permanent.

Official Title
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Kisspeptin in the Evaluation of Delayed Puberty

Conditions
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Hypogonadotropic Hypogonadism, GnRH Deficiency, Kallmann Syndrome, Delayed Puberty

Intervention / Treatment
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* Drug: kisspeptin 112-121
* Drug: GnRH


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adolescent Boys ages 13.5-17 years testicular volume <4 mL OR 4-8 ml with no change in the past 6 months by Prader orchidometer first morning (before 9AM) LH <2 mIU/mL and testosterone <50 ng/dL Adolescent Girls ages 12-17 years Tanner stage I OR II breast development with no change in the past 6 months first morning (before 9AM) LH <2 mIU/mL and estradiol <20 pg/ml All Subjects: bone age less than chronological age weight ≥ 28 kg body mass index >10th percentile and <+3 SDS for bone age blood pressure >5th percentile and <95th percentile for bone age and height white blood cell counts, platelet counts, electrolytes, thyroid stimulating hormone (TSH), free thyroxine (T4) within reference range for age erythrocyte sedimentation rate <2X the upper limit of the reference range for age hemoglobin within reference range for girls of the same chronological age blood urea nitrogen (BUN), creatinine, prolactin not elevated aspartate aminotransferase (AST) and alanine aminotransferase (ALT) no more than 2X the upper limit of the reference range Insulin-like growth factor 1 (IGF-1) within reference range for bone age Exclusion Criteria: All Subjects: history or presence of underlying condition that could cause delayed puberty (chronic illness, weight loss, abnormal cranial magnetic resonance imaging (MRI)) history of an allergic drug reaction

Ages Eligible for Study
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Minimum Age: 12 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Kisspeptin, GnRH<br>Intravenous (IV) administration of kisspeptin 112-121 0.24 nmol/kg and GnRH 75 ng/kg | Drug: kisspeptin 112-121<br>* 0.24 nmol/kg<br>* Other names: metastin 45-54;Drug: GnRH<br>* 75 ng/kg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average change in luteinizing hormone (LH) in response to kisspeptin |  | Within 30 minutes of administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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delayed puberty, Kallmann Syndrome, Hypogonadotropic hypogonadism, GnRH Deficiency, kisspeptin, GnRH