Effect of Adrenocorticotropic Hormone on Vascular Endothelial Growth Factor Release in Children Study

NCT03709381 | Completed Early Phase 1 FDA Drug

• 1 other identifier: IRB17-00194
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

Bone disease and adrenal suppression are two of the many side effects of steroid use in pediatrics. Evidence has shown that adrenocorticotropic hormone (ACTH) protects against the adverse bone effects of steroids in animals and in vitro models, but this has not yet been evaluated in humans. The proposed mechanism in these studies is that ACTH stimulates osteoblasts in bone to release Vascular Endothelial Growth Factor (VEGF), which increases the vascularity in high risk areas of bone. This can potentially be protective against osteonecrosis and osteopenia, which can lead to bone fractures if not prevented. The VEGF release can also be used to demonstrate that an administration of exogenous ACTH occurred. This could be important in diagnosing adrenal insufficiency (AI). One of the tests to assess central AI is the low-dose ACTH stimulation test (LDAST). This test has a high rate of false positive results due to technical limitations. However, if an ACTH-stimulated VEGF level can be measured during the test as a marker of the test being done properly, it will allow for proper interpretation of the results (and identification of a false positive), which will reduce the number of patients being incorrectly diagnosed with central AI. This study will recruit ten healthy children and adolescents, ages 9-18, to assess the effects of ACTH on VEGF levels. The investigators will measure the response of VEGF and cortisol to an administration of a low dose and high dose of cosyntropin (the synthetic ACTH analog used in this test). The hypothesis of this study is that VEGF and cortisol will both increase after administration of cosyntropin. At this time, no other studies have demonstrated that VEGF is responsive to ACTH in humans. If the hypothesis is correct, the results will have two main implications. VEGF can be used as a marker of ACTH administration during the LDAST to identify false positive tests. Secondly, this will help further research into whether ACTH can be used to protect against bone disease in high-dose steroid-treated patients. Further studies can be done to assess whether this effect will be the same in patients with AI or steroid-induced adrenal suppression.

Conditions

Adrenal Insufficiency; Osteopenia, Osteoporosis; Steroid Suppression of ACTH Secretion

Keywords

steroid-induced adrenal suppression; vascular endothelial growth factor; adrenocorticotropic hormone; osteopenia

Outcome Measures

Primary Outcomes (1)

• Difference between VEGF levels at baseline and the peak VEGF level after low dose cosyntropin administration in healthy children and adolescents

  Prior to administering Cosyntropin, a VEGF level will be obtained. 1 mcg Cosyntropin will be administered at t=0, then VEGF will be measured at 30 and 60 minutes. The investigators will run a comparison on the peak plasma VEGF level (the higher of the 30 and 60 minute level) after low dose stimulation compared to baseline VEGF levels.

  From t=0 minutes to t=60 minutes (1 hour total)

Secondary Outcomes (1)

• Difference between VEGF levels at baseline and the peak VEGF level after high dose cosyntropin administration in healthy children and adolescents

  From t=60 minutes to t=180 minutes (2 hours total)

Study Arms (1)

ACTH stim test arm

EXPERIMENTAL

Cosyntropin 1 mcg IV (low dose) will be given to subjects at t=0 minutes, and Cosyntropin 250 mcg (high dose) IV will be given to subjects at t=60 minutes. (All subjects were in the same arm and had the same protocol).

Drug: Low Dose Cosyntropin (ACTH) stimulation test; Drug: High Dose Cosyntropin (ACTH) stimulation test

Interventions

Low Dose Cosyntropin (ACTH) stimulation test DRUG

Cosyntropin 1 mcg IV given to subjects at t=0

ACTH stim test arm

High Dose Cosyntropin (ACTH) stimulation test DRUG

Cosyntropin 250 mcg IV given to subjects at t=60

ACTH stim test arm

Eligibility Criteria

• Age: 9 Years - 17 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Subjects will be between the ages of 9-18 years old on the day of testing

You may not qualify if:

• Currently taking any medication other than over-the-counter medications (over-the-counter medications will be stopped on the day of the study)
• Steroid use within the prior six months (including IV, oral, inhaled, and intranasal steroids)
• Oral Contraceptive Pill use within the prior six months
• Any chronic medical conditions
• Pregnancy

Sponsors & Collaborators

• Nationwide Children's Hospital: lead

Study Sites (1)

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

MeSH Terms

Conditions

Adrenal Insufficiency; Bone Diseases, Metabolic

Interventions

Cosyntropin; Adrenocorticotropic Hormone

Condition Hierarchy (Ancestors)

Adrenal Gland Diseases; Endocrine System Diseases; Bone Diseases; Musculoskeletal Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Melanocortins; Pro-Opiomelanocortin; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Pituitary Hormones, Anterior; Pituitary Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Nerve Tissue Proteins; Proteins

Study Officials

• Ryan Heksch, MD

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Fellow

Model Details: At t=0, 9 ml of blood will be collected for measurement of VEGF, ACTH, and cortisol levels. Then, 1 mcg of cosyntropin (a synthetic ACTH analog) will be administered intravenously (IV). Samples for measurement of cortisol and VEGF levels will be obtained at t=30 and 60 minutes (6 ml of blood collected at both times). After the 60 minute blood draw, 250 mcg of cosyntropin will be administered IV. At t=90, 120, 150 , and 180 minutes, samples for measurement of cortisol and VEGF levels will be obtained (6 ml of blood collected at each time).

Study Record Dates

• First Submitted: October 2, 2017
• First Posted: October 17, 2018
• Study Start: October 1, 2017
• Primary Completion: October 31, 2018
• Study Completion: January 31, 2019
• Last Updated: February 21, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)