Kisspeptin in the Evaluation of Delayed Puberty

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.

Study Overview

• Status: Completed
• Conditions: Kallmann Syndrome; Hypogonadotropic Hypogonadism; Delayed Puberty; GnRH Deficiency
• Intervention / Treatment: Drug: kisspeptin 112-121; Drug: GnRH

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.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Study Coordinator; Phone Number: 617-643-2308; Email: MGHKisspeptinResearch@partners.org

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 15 years (Child)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Investigators: Principal Investigator: Stephanie B Seminara, MD, Massachusetts General Hospital

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): June 8, 2013
• Primary Completion (Actual): September 8, 2019
• Study Completion (Actual): September 10, 2021

Study Registration Dates

• First Submitted: August 24, 2011
• First Submitted That Met QC Criteria: September 20, 2011
• First Posted (Estimated): September 21, 2011

Study Record Updates

• Last Update Posted (Actual): October 19, 2023
• Last Update Submitted That Met QC Criteria: October 17, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: kisspeptin; GnRH; Kallmann Syndrome; GnRH Deficiency; Hypogonadotropic hypogonadism; delayed puberty
• Additional Relevant MeSH Terms: Endocrine System Diseases; Gonadal Disorders; Disorders of Sex Development; Urogenital Abnormalities; Congenital Abnormalities; Genetic Diseases, Inborn; Disorder of Sex Development, 46,XY; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Kallmann Syndrome; Hypogonadism; Puberty, Delayed
• Other Study ID Numbers: 2011P002885

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No