Free Fatty Acids, Body Weight, and Growth Hormones Secretion in Children

NCT01237041 | Terminated Phase 1 Results DMC FDA Drug

• 2 other identifiers: 11000411-CH-0004
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

Background: \- Overweight and obese children and adults often have lower levels of growth hormone in the blood. Regulation of growth hormone may be tied to weight and free fatty acids in the blood. Current tests of growth hormone (such as those used when evaluating the heights of children who are markedly shorter than other children of comparable age) may be affected by other factors, including obesity. Researchers are interested in evaluating the levels of growth hormone and free fatty acids in the blood of children between 7 and 14 years of age who weigh more than children of a comparable age, or who are shorter than other children of a comparable age and have been recommended for growth hormone testing as part of an evaluation for their height. Objectives: \- To determine the effect of changes in free fatty acids in the blood on changes in growth hormone secretion in overweight or shorter children and young adolescents. Eligibility: \- Children and adolescents between 7 and 14 years of age who weigh more than or are shorter than other children of a comparable age and do not have any medical illnesses. Design:

• Participants will have two study visits, one of which will be a half day screening visit in the outpatient clinic and one of which will require 2 nights as an inpatient at the National Institutes of Health Clinical Center.
• Participants should not eat or drink anything except water after 10 PM the night before or on the morning of the screening visit.
• At the screening visit, participants will have a physical examination and medical history, provide blood and urine samples, have an oral glucose tolerance test (to check blood sugar levels), and have an x-ray of the left hand to check bone age.
• The inpatient study visit will involve a physical examination and medical history, a full x-ray scan to study body fat and muscle, frequent blood tests throughout the visit, and various medications to stimulate growth hormone production and lower levels of free fatty acids in the blood.

Conditions

Obesity; Short Stature; Growth Hormone Deficiency

Keywords

Child; Body Fat; Niacin; Growth Hormone; Obesity; Overweight; Growth Hormones; Short Stature; Children

Outcome Measures

Primary Outcomes (1)

• Growth Hormone Secretion Area Under the Curve in Response to Niacin and Placebo Over Time

  Growth hormone Area Under the Curve in response to niacin versus placebo over 4 hours. For growth hormone, samples collected at 0, 30, 60, 90, 120, 150, 180, 210, and 240 minutes.

  4 hours

Secondary Outcomes (3)

• Free Fatty Acids (FFA) Area Under the Curve in Response to Niacin and Placebo Over 4 Hours

  4 hours

• Growth Hormone-releasing Hormone (GHRH) Area Under the Curve in Response to Niacin and Placebo Over 4 Hours

  4 hours

• Somatostatin (SST) Area Under the Curve in Response to Niacin and Placebo Over 4 Hours

  4 hours

Study Arms (5)

Niacin First

EXPERIMENTAL

Subjects receive niacin 500mg hourly for 4 hours on day 1 (at 7:30am, 8:30am, 9:30am, and 10:30am) then cross over to receive placebo hourly for 4 hours on day 2 at (7:30am, 8:30am, 9:30am, and 10:30am).

Drug: Niacin First; Drug: Placebo First

Placebo First

EXPERIMENTAL

Subjects receive placebo hourly for 4 hours on day 1 (at 7:30am, 8:30am, 9:30am, and 10:30am) then cross over to receive niacin hourly for 4 hours on day 2 (at 7:30am, 8:30am, 9:30am, and 10:30am).

Drug: Niacin First; Drug: Placebo First

Dose-Establishing Study 1 Niacin 250mg

EXPERIMENTAL

Subjects received Niacin 250 mg every 2 hours for 3 doses (at 6am, 8am, and 10am).

Drug: Dose-Establishing Study 1 Niacin 250mg

Dose-Establishing Study 1 Niacin 500mg

EXPERIMENTAL

Subjects received Niacin 500 mg every 2 hours for 3 doses (at 6am, 8am, and 10am).

Drug: Dose-Establishing Study 1 Niacin 500mg

Dose-Establishing Study 2 Niacin 500mg

EXPERIMENTAL

Subjects received Niacin 500 mg hourly for 4 doses (administered at 7:30am, 8:30am, 9:30am, and 10:30am).

Drug: Dose-Establishing Study 2 Niacin 500mg

Interventions

Niacin First DRUG

Niacin 500 mg po four times on one of the inpatient days, then placebo on another inpatient day

Also known as: RCT Niacin First

Niacin First; Placebo First

Placebo First DRUG

Placebo po four times on one of the inpatient days, then Niacin 500 mg po four times on another inpatient day

Also known as: RCT Placebo First

Niacin First; Placebo First

Dose-Establishing Study 1 Niacin 250mg DRUG

Niacin 250 mg po three times at 2 hour intervals on an inpatient day

Also known as: Open-Label Niacin 250mg x 3 doses

Dose-Establishing Study 1 Niacin 250mg

Dose-Establishing Study 1 Niacin 500mg DRUG

Niacin 500 mg po three times at 2 hour intervals on an inpatient day

Also known as: Open-Label Niacin 500mg x 3 doses

Dose-Establishing Study 1 Niacin 500mg

Dose-Establishing Study 2 Niacin 500mg DRUG

Open-Label Niacin 500mg four times at 1 hour intervals on an inpatient day

Also known as: Open-Label Niacin 500mg x four doses

Dose-Establishing Study 2 Niacin 500mg

Eligibility Criteria

• Age: 7 Years - 14 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Subjects will qualify for the overweight group for the dose-establishing studies 1 and 2 and main study) if they meet the following criteria:
• Good general health.
• Age greater than or equal to 7 and less than 15 years.
• Tanner stage I, II or III for the breast among girls and testes less than10 mL for boys based upon an examination by a trained physician or nurse practitioner.
• Weight \> 30 kg.
• Fasting plasma glucose \< 100 mg/dL, 2 hour post-dextrose glucose \< 140 mg/dL, and HgbA1C less than or equal to 6.4%.
• Females who are age 10 or greater must have a negative pregnancy test.
• Body mass index greater than or eqaul to 95th percentile determined by Centers for Disease Control age and sex specific data (given that most pathology of obesity does not usually emerge until children cross the 95th percentile).
• No evidence of growth failure as defined as height \> 5th percentile.
• Subjects will qualify for the non-overweight control group (for the main study only) if they meet the following criteria:
• Recommended by a pediatric endocrinologist to undergo GH stimulation testing to establish the diagnosis of GH-deficiency.
• Good general health.
• Age greater than or equal to 7 and less than15 years.
• Tanner stage I, II or III for the breast among girls and testes less than 10 mL for boys based upon an examination by a trained physician or nurse practitioner.
• Weight \> 30 kg.

You may not qualify if:

• Subjects will be excluded if they have any of the following:
• Baseline creatinine greater than or equal to 1.0 mg/dl.
• Significant cardiac or pulmonary disease likely to or resulting in hypoxia or decreased perfusion.
• Hepatic disease with elevated liver function tests (ALT or AST)greater than or equal to 1.5 the upper limits of normal.
• Pregnancy.
• Evidence for impaired glucose tolerance or Type 2 diabetes, including fasting plasma glucose greater than or equal to 100 mg/dL, 2 hour post-dextrose glucose greater than or equal to 140 mg/dL, or HgbA1C \> 6.4%.
• Presence of other endocrinologic disorders leading to obesity (e.g. Cushing Syndrome).
• Any disorder that is known to affect GH secretion (e.g. untreated hypothyroidism) or use of any medication known to affect GH levels (including glucocorticoids and GH itself).
• Any other disorder that is known to affect stature including skeletal dysplasias.
• Recent use (within two years) of anorexiant medications, stimulant medications, or other medications felt to impact growth.
• Individuals who have, or whose parent or guardians have, current substance abuse or a psychiatric disorder or other condition that, in the opinion of the investigators, would impede competence or compliance or possibly hinder completion of the study.
• Individuals receiving medical treatment other than diet for hypertension or dyslipidemia.
• Individuals with evidence of precocious puberty as defined as palpable breast tissue noted in females before the age of 7, testicular size greater than or equal to 4cc in males before the age of 9, or bone age advancement more than 2 SD for chronologic age.
• Individuals receiving androgen or estrogen hormone therapy.

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Tauber M, Moulin P, Pienkowski C, Jouret B, Rochiccioli P. Growth hormone (GH) retesting and auxological data in 131 GH-deficient patients after completion of treatment. J Clin Endocrinol Metab. 1997 Feb;82(2):352-6. doi: 10.1210/jcem.82.2.3726.

  PMID: 9024217 BACKGROUND

• Cohen P, Rogol AD, Deal CL, Saenger P, Reiter EO, Ross JL, Chernausek SD, Savage MO, Wit JM; 2007 ISS Consensus Workshop participants. Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop. J Clin Endocrinol Metab. 2008 Nov;93(11):4210-7. doi: 10.1210/jc.2008-0509. Epub 2008 Sep 9.

  PMID: 18782877 BACKGROUND

• Zucchini S, Pirazzoli P, Baronio F, Gennari M, Bal MO, Balsamo A, Gualandi S, Cicognani A. Effect on adult height of pubertal growth hormone retesting and withdrawal of therapy in patients with previously diagnosed growth hormone deficiency. J Clin Endocrinol Metab. 2006 Nov;91(11):4271-6. doi: 10.1210/jc.2006-0383. Epub 2006 Aug 15.

  PMID: 16912138 BACKGROUND

• Galescu OA, Crocker MK, Altschul AM, Marwitz SE, Brady SM, Yanovski JA. A pilot study of the effects of niacin administration on free fatty acid and growth hormone concentrations in children with obesity. Pediatr Obes. 2018 Jan;13(1):30-37. doi: 10.1111/ijpo.12184. Epub 2016 Sep 21.

  PMID: 27654882 BACKGROUND

MeSH Terms

Conditions

Obesity; Dwarfism; Dwarfism, Pituitary; Overweight

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Endocrine System Diseases; Bone Diseases, Endocrine; Hypopituitarism; Pituitary Diseases; Hypothalamic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Dr. Jack Yanovski
• Organization: NICHD, National Institutes of Health

yanovskj@mail.nih.gov

13014960858

Study Officials

• Jack A Yanovski, M.D.

  Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Masking only during the two arms of the randomized trial portion of the study, not during the dose-finding arms.
• Purpose: DIAGNOSTIC
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Section on Growth and Obesity

Model Details: First, we conducted dose-establishing studies using 250mg every 2 hours x 3 doses (2 subjects), 500mg every two hours x 3 doses (5 subjects), and 500mg hourly x 4 doses (5 subjects). This dose-establishing study was followed by the randomized crossover trial using 500mg hourly x 4 doses in conjunction with growth hormone stimulation testing. The RCT was terminated early because of inability to obtain necessary study medications.

Study Record Dates

• First Submitted: November 6, 2010
• First Posted: November 9, 2010
• Study Start: July 1, 2011
• Primary Completion: October 17, 2017
• Study Completion: December 13, 2017
• Last Updated: December 17, 2018
• Results First Posted: December 17, 2018

Record last verified: 2018-12

Locations

US (1)