The AgRP and GH/IGF-1 Axis in Children

Agouti-related Peptide (AgRP) and the GH/IGF-1 Axis in Children

Recent data support the existence of a GH-Agouti-related peptide (AgRP) axis. The neuropeptide AgRP promotes food intake and has important effects on energy homeostasis. Recent evidence suggest that GH stimulates AgRP and AgRP may mediate some of GH's important nutritional and metabolic effects. main goals of this project are to characterize, for the first time, plasma levels of AgRP in children and to determine how these relate to GH and IGF-1 levels, age, body composition, clinical and other endocrine parameters. To accomplish this, we will conduct two studies, one being a cross-sectional study that will measure AgRP levels in 140 healthy children ages 5-17 and the second being a prospective study that will measure the change in plasma AgRP levels in response to GH treatment in 16 children who receive this as part of their clinical care for GH deficiency or short stature.

Study Overview

• Status: Not yet recruiting
• Conditions: Growth Hormone Deficiency

Detailed Description

Protocol 1 This will be a cross-sectional study in 140 healthy children. Participation will include one visit that will take place between 8-9 am and after a fast from midnight the night before.

Procedures at the visit will include:

1. Review of medical history
2. Anthropometrics measurements: Weight, height, waist and hip circumferences.
3. Collection of information from medical record including growth records and physical examination findings including features relevant to pubertal stage in all children and onset of menses in females.
4. Assessment of pubertal status and Tanner stage based on physical examination.
5. Collection of information on diet, activity level and sleep.
6. Blood Sampling: venous blood will be sampled from a peripheral vein for measurement of AgRP, GH, IGF-1, leptin, SOb-R, triglycerides, insulin, glucose, testosterone(males), estradiol(females), DHEAS and cortisol levels. Insulin and glucose levels will be used to assess insulin resistance by HOMA & QUICKI.

Protocol 2 This will be a prospective study in 16 children who will be studied before and at 4 time points (1 week, 2 weeks, 1 month and 2 months) after starting GH treatment as part of their clinical care. This protocol will study subjects Groups 2 and 3. Growth hormone will not be prescribed as part of this study. Children will be treated clinically with GH as prescribed by their Pediatric Endocrinologist for FDA approved indications and according to standard guidelines for dosing for treatment of GH deficiency in children.

Each visit that will take place between 8-9 am and after a fast from midnight the night before.

Procedures at each visit will include:

1. Review of medical history
2. Anthropometrics measurements: Weight, height, waist and hip circumferences, skinfold thicknesses.
3. Collection of information from medical record including growth records and physical examination findings including features relevant to pubertal stage in all children and onset of menses in females. GH dose and compliance will be recorded at follow up visits.
4. Collection of information on diet, activity level and sleep.
5. Blood Sampling: Venous blood will be sampled at a peripheral vein for:

Baseline (pre-GH treatment): measurement of AgRP, GH, IGF-1, IGFBP-3, leptin, SOb-R, triglycerides, insulin and glucose, testosterone(males), estradiol(females), DHEAS and cortisol levels.

Follow up visits on growth hormone: measurement of AgRP, IGF-1, IGFBP-3, leptin, SOb-R, triglycerides, insulin, glucose and cortisol levels.

Insulin and glucose levels will be used to assess insulin resistance by HOMA & QUICKI.

• Study Type: Observational
• Enrollment (Estimated): 156

Contacts and Locations

• Study Contact: Name: Pamela Freda; Phone Number: 2123052254; Email: puf1@cumc.columbia.edu
• Study Contact Backup: Name: Rosa Lazarte; Phone Number: 2123054921; Email: rl2345@cumc.columbia.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 17 years (Child)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Healthy children: 140 healthy children (70 females and 70 males) between the ages of 5-17 yr. will be studied; 7-8 children per year of this age range will be studied. They will be representative of the diverse racial and ethnic mix of children who receive their medical care at our medical center.Children will be recruited from among the healthy children visiting primary care Pediatricians at our medical center.

GH deficient and idiopathic short stature children: 16 children (8 males, 8 females) between the ages of 5 - 9 yr. who are pre-pubertal and who plan to start GH treatment for isolated GH deficiency or idiopathic short stature. They will be representative of the diverse racial and ethnic mix of our hospital's patient population.

Description

Healthy children

Inclusion Criteria:

1. Ambulatory male and female children aged 5-17 years
2. Normal weight at birth
3. Height between the 3rd and 99th percentiles of the mean as per the CDC growth percentiles.

Exclusion Criteria:

1. Genetic defects, chronic illnesses.
2. Current prescription medication use
3. Use of glucocorticoids, thyroid hormone or medications that may affect the GH-IGF-1 axis within 6 months of study entry.

Children with GH deficiency:

Inclusion Criteria:

1. Ambulatory male and female children aged 5-9 years who are prepubertal
2. Normal weight at birth
3. Growth failure
4. Peak GH response to 2 GH stimulation tests < 10 ng/ml
5. Normal renal and liver function

Exclusion criteria:

1. Multiple pituitary hormone deficiencies,
2. GH deficiency or poor growth associated with any acute or chronic medical condition such as renal disease or Turner's syndrome.
3. History of diabetes or malignancy
4. Use of glucocorticoids or medications known to affect the GH-IGF-1 axis within 6 months of study entry.

Children with idiopathic Short Stature:

Inclusion Criteria:

1. Ambulatory male and female children aged 5-9 years who are prepubertal
2. Normal weight at birth
3. Height >2.25 SD below mean for age
4. Peak GH response to 2 stimulation tests >10 ng/ml or normal IGF-1 and IGFBP-3 levels
5. No prior supplemental growth hormone exposure
6. Normal renal and liver function

Exclusion criteria:

1. Poor growth associated with any acute or chronic medical condition such as renal disease or Turner's syndrome.
2. History of diabetes or malignancy
3. Use of glucocorticoids or medications known to affect the GH-IGF-1 axis within 6 months of study entry.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort
Group 1: Healthy children; 140 healthy children (70 females and 70 males) between the ages of 5-17 yr. will be studied; 7-8 children per year of this age range will be studied. They will be representative of the diverse racial and ethnic mix of children who receive their medical care at our medical center. Inclusion Criteria: Ambulatory male and female children aged 5-17 years; Normal weight at birth; Height between the 3rd and 99th percentiles of the mean as per the CDC growth percentiles. Exclusion Criteria: Genetic defects, chronic illnesses.; Current prescription medication use; Use of glucocorticoids, thyroid hormone or medications that may affect the GH-IGF-1 axis within 6 months of study entry.
Group 2: Children with GH deficiency; 16 children (8 males, 8 females) between the ages of 5 - 9 yr. who are pre-pubertal and who plan to start GH treatment for isolated GH deficiency or idiopathic short stature. They will be representative of the diverse racial and ethnic mix of our hospital's patient population. GH deficiency: Inclusion Criteria: Ambulatory male and female children aged 5-9 years who are prepubertal; Normal weight at birth; Growth failure; Peak GH response to 2 GH stimulation tests < 10 ng/ml; Normal renal and liver function Exclusion criteria: Multiple pituitary hormone deficiencies,; GH deficiency or poor growth associated with any acute or chronic medical condition such as renal disease or Turner's syndrome.; History of diabetes or malignancy; Use of glucocorticoids or medications known to affect the GH-IGF-1 axis within 6 months of study entry.
Group 3: Children with short stature; Idiopathic Short Stature: Inclusion Criteria: Ambulatory male and female children aged 5-9 years who are prepubertal; Normal weight at birth; Height >2.25 SD below mean for age; Peak GH response to 2 stimulation tests >10 ng/ml or normal IGF-1 and IGFBP-3 levels; No prior supplemental growth hormone exposure; Normal renal and liver function Exclusion criteria: Poor growth associated with any acute or chronic medical condition such as renal disease or Turner's syndrome.; History of diabetes or malignancy; Use of glucocorticoids or medications known to affect the GH-IGF-1 axis within 6 months of study entry.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Protocol 1: Correlation of Plasma AgRP levels with IGF-1 levels	Plasma AgRP levels correlation with IGF-1 levels Protocol 1: Correlation of Plasma AgRP levels with IGF-1 levels	Baseline (cross-sectional at single time point, no intervention)
Protocol 2: Change in plasma AgRP levels with GH therapy	Change in plasma AgRP levels from pre-GH therapy to post-GH therapy	baseline to 2 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Protocol 1: Correlation of plasma AgRP levels with age	Correlation of plasma AgRP levels with age	Baseline (cross-sectional testing at one time point, no intervention)
Protocol 1: Correlation of plasma AgRP levels with leptin levels	Correlation of plasma AgRP levels with leptin levels	Baseline (cross-sectional testing at one time point, no intervention)
Protocol 1: Correlation of plasma AgRP with percent body fat (determined from skinfold thickness)	Correlation of plasma AgRP with percent body fat (determined from skinfold thickness)	Baseline (cross-sectional testing at one time point, no intervention)
Protocol 2: Change in AgRP levels correlation with change in IGF-1 levels	Correlation of change in AgRP levels with change in IGF-1 levels from baseline to 2 months of GH therapy	Baseline to 2 months
Protocol 2: Change in AgRP level correlation with pre-treatment leptin levels	Correlation of change in AgRP level from baseline to 2 months of GH therapy with pre-treatment leptin levels	Baseline to 2 months

Collaborators and Investigators

• Sponsor: Columbia University

Study record dates

Study Major Dates

• Study Start (Estimated): June 10, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: November 30, 2022
• First Submitted That Met QC Criteria: December 8, 2022
• First Posted (Actual): December 9, 2022

Study Record Updates

• Last Update Posted (Estimated): August 26, 2025
• Last Update Submitted That Met QC Criteria: August 25, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Endocrine System Diseases; Bone Diseases; Musculoskeletal Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypothalamic Diseases; Pituitary Diseases; Bone Diseases, Endocrine; Bone Diseases, Developmental; Dwarfism; Hypopituitarism; Dwarfism, Pituitary
• Other Study ID Numbers: AAAU4134

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