Anaplerotic Therapy Using Triheptanoin for Patients With Glycogen Storage Disease Type I

NCT03665636 | Completed Early Phase 1 DMC FDA Drug

• 1 other identifier: Pro00103582
• Study Type: interventional
• Target: 4
• Locations: 1 country
• Sites: 1

Brief Summary

This study will be an open-label, prospective, interventional feasibility pilot project to study the efficacy, safety, and tolerability of UX007 (triheptanoin) on reducing hypoglycemic events in patients with GSD I. Subjects will serve as their own control. Five (5) subjects who are treatment naïve to UX007 (triheptanoin) and are already on standard dietary therapy for GSDI will be enrolled. The primary objective is to evaluate the efficacy, safety, and tolerability of UX007 (triheptanoin) in patients with GSD I. The secondary objectives include evaluating the effect of UX007 (triheptanoin) on maintaining the duration of normoglycemia between meals based on glucose monitoring (Preventing and reducing the frequency of hypoglycemia); reduction/stabilization of the dose of cornstarch; and the prevention of increased liver steatosis based on ultrasound with elastography.

Conditions

Glycogen Storage Disease Type I

Keywords

Glycogen Storage Disease Type I; GSD I; Anaplerosis; Triheptanoin; Hypoglycemia

Outcome Measures

Primary Outcomes (1)

• Blood glucose level

  Reviewing the change in blood glucose levels from baseline to 6 month visit

  Baseline and 6 months

Secondary Outcomes (5)

• Dietary intake

  Baseline and 6 months

• Liver steatosis assessment

  Baseline and 6 months

• Liver size assessment

  Baseline and 6 months

• Laboratory metabolic control markers

  Baseline and 6 months

• Other laboratory metabolic control markers

  Baseline and 6 months

Study Arms (1)

Triheptanoin

EXPERIMENTAL

Open Label Study

Drug: Triheptanoin

Interventions

Triheptanoin DRUG

This is an open-label study. The UX007 (triheptanoin) starting dose will be 0.25 - 0.5 g/kg and titrated to a maximum of 2.5g/kg depending the on the subject's tolerance. The dose may be reduced if not tolerated. The compound will be administered 3-4 times per day, either at the end of a meal or with a snack. It should be given at least 2 hours apart from any cornstarch dose to allow each to act independent of one another, and to prevent the risk of increased gastrointestinal side effects. The doses may be held during episodes of gastroenteritis or diarrhea.

Also known as: UX007

Triheptanoin

Eligibility Criteria

• Age: 1 Month - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Naive to UX007 (triheptanoin)
• Confirmed documented diagnosis of GSDI: confirmation may be based on mutation analysis, liver biopsy, or enzyme testing
• Willing and able to complete all aspects of the study through the end of the study, including visits and tests, documentation of symptoms, blood sugar and dietary log, and administration of UX007 (triheptanoin); minors in the study must have a parent/legally authorized representative who is willing and able to assist in all applicable study requirements

You may not qualify if:

• Have a history of severe inflammatory bowel disease, or severe chronic diarrhea per the PI discretion on conventional doses of cornstarch
• Patient is on any other form of medium chain triglyceride (MCT) during the time of the study. Patients will be asked to stop any nutritional compound that includes MCT oil one week (7 days) prior to baseline.
• Have any co-morbid conditions, including major organ-system disease(s) that in the opinion of the Investigator, places the subject at increased risk of complications, interferes with study participation or compliance, or confounds study objectives
• Pregnancy
• Patients on continuous feeds, with a diagnosis of diabetes, and/or a diagnosis of any other inborn error or metabolism

Sponsors & Collaborators

• Areeg El-Gharbawy: lead
• Ultragenyx Pharmaceutical Inc: collaborator

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Related Publications (8)

• Chou JY, Matern D, Mansfield BC, Chen YT. Type I glycogen storage diseases: disorders of the glucose-6-phosphatase complex. Curr Mol Med. 2002 Mar;2(2):121-43. doi: 10.2174/1566524024605798.

  PMID: 11949931 BACKGROUND

• Fernandes J, Pikaar NA. Ketosis in hepatic glycogenosis. Arch Dis Child. 1972 Feb;47(251):41-6. doi: 10.1136/adc.47.251.41.

  PMID: 4336232 BACKGROUND

• Rasmussen BB, Holmback UC, Volpi E, Morio-Liondore B, Paddon-Jones D, Wolfe RR. Malonyl coenzyme A and the regulation of functional carnitine palmitoyltransferase-1 activity and fat oxidation in human skeletal muscle. J Clin Invest. 2002 Dec;110(11):1687-93. doi: 10.1172/JCI15715.

  PMID: 12464674 BACKGROUND

• Das AM, Lucke T, Meyer U, Hartmann H, Illsinger S. Glycogen storage disease type 1: impact of medium-chain triglycerides on metabolic control and growth. Ann Nutr Metab. 2010;56(3):225-32. doi: 10.1159/000283242. Epub 2010 Mar 30.

  PMID: 20357432 BACKGROUND

• Nagasaka H, Hirano K, Ohtake A, Miida T, Takatani T, Murayama K, Yorifuji T, Kobayashi K, Kanazawa M, Ogawa A, Takayanagi M. Improvements of hypertriglyceridemia and hyperlacticemia in Japanese children with glycogen storage disease type Ia by medium-chain triglyceride milk. Eur J Pediatr. 2007 Oct;166(10):1009-16. doi: 10.1007/s00431-006-0372-0. Epub 2007 Jan 6.

  PMID: 17206455 BACKGROUND

• Gu L, Zhang GF, Kombu RS, Allen F, Kutz G, Brewer WU, Roe CR, Brunengraber H. Parenteral and enteral metabolism of anaplerotic triheptanoin in normal rats. II. Effects on lipolysis, glucose production, and liver acyl-CoA profile. Am J Physiol Endocrinol Metab. 2010 Feb;298(2):E362-71. doi: 10.1152/ajpendo.00384.2009. Epub 2009 Nov 10.

  PMID: 19903863 BACKGROUND

• Farah BL, Sinha RA, Wu Y, Singh BK, Lim A, Hirayama M, Landau DJ, Bay BH, Koeberl DD, Yen PM. Hepatic mitochondrial dysfunction is a feature of Glycogen Storage Disease Type Ia (GSDIa). Sci Rep. 2017 Mar 20;7:44408. doi: 10.1038/srep44408.

  PMID: 28317891 BACKGROUND

• Roe CR, Mochel F. Anaplerotic diet therapy in inherited metabolic disease: therapeutic potential. J Inherit Metab Dis. 2006 Apr-Jun;29(2-3):332-40. doi: 10.1007/s10545-006-0290-3.

  PMID: 16763896 BACKGROUND

MeSH Terms

Conditions

Glycogen Storage Disease Type I; Hypoglycemia

Interventions

triheptanoin

Condition Hierarchy (Ancestors)

Glycogen Storage Disease; Carbohydrate Metabolism, Inborn Errors; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Glucose Metabolism Disorders

Study Officials

• Areeg El-Gharbawy, MD

  Duke University, Department of Pediatrics - Medical Genetics

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Assistant Professor of Pediatrics

Model Details: This study is an interventional, open-label, feasibility pilot project to study the safety, efficacy, and tolerability of triheptanoin in patients with GSD I.

Study Record Dates

• First Submitted: August 23, 2018
• First Posted: September 11, 2018
• Study Start: October 16, 2020
• Primary Completion: October 21, 2021
• Study Completion: October 21, 2021
• Last Updated: December 15, 2021

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)