Kisspeptin in the Evaluation of Delayed Puberty

NCT ID: NCT01438034

Last Updated: 2023-10-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-06-08
• Study Completion Date: 2021-09-10

Brief Summary

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

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.

Conditions

Delayed Puberty; Kallmann Syndrome; Hypogonadotropic Hypogonadism; GnRH Deficiency

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

Kisspeptin, GnRH

Intravenous (IV) administration of kisspeptin 112-121 0.24 nmol/kg and GnRH 75 ng/kg

Group Type: EXPERIMENTAL

kisspeptin 112-121

Intervention Type: DRUG

0.24 nmol/kg

GnRH

Intervention Type: DRUG

75 ng/kg

Interventions

kisspeptin 112-121

0.24 nmol/kg

Intervention Type: DRUG

GnRH

75 ng/kg

Intervention Type: DRUG

Other Intervention Names

metastin 45-54

Eligibility Criteria

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

• Minimum Eligible Age: 12 Years
• Maximum Eligible Age: 17 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Stephanie B. Seminara, MD

Chief, Reproductive Endocrine Unit; Professor of Medicine, Harvard Medical School; Director, MGH Harvard Center for Reproductive Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Stephanie B Seminara, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

References

Chan YM, Lippincott MF, Sales Barroso P, Alleyn C, Brodsky J, Granados H, Roberts SA, Sandler C, Srivatsa A, Seminara SB. Using Kisspeptin to Predict Pubertal Outcomes for Youth With Pubertal Delay. J Clin Endocrinol Metab. 2020 Aug 1;105(8):e2717-25. doi: 10.1210/clinem/dgaa162.

Reference Type: DERIVED

PMID: 32232399 (View on PubMed)

Chan YM, Lippincott MF, Kusa TO, Seminara SB. Divergent responses to kisspeptin in children with delayed puberty. JCI Insight. 2018 Apr 19;3(8):e99109. doi: 10.1172/jci.insight.99109. eCollection 2018 Apr 19.

Reference Type: DERIVED

PMID: 29669934 (View on PubMed)

Other Identifiers

2011P002885

Identifier Type: -

Identifier Source: org_study_id