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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03665636
Recruitment Status : Recruiting
First Posted : September 11, 2018
Last Update Posted : May 5, 2020
Sponsor:
Collaborator:
Ultragenyx Pharmaceutical Inc
Information provided by (Responsible Party):
Areeg El-Gharbawy, Duke University

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.


Condition or disease Intervention/treatment Phase
Glycogen Storage Disease Type I Drug: Triheptanoin Early Phase 1

Detailed Description:

Prior to first study appointment:

A medical record review will be done prior to the appointment to confirm the diagnosis of GSD I. For interested subjects who are not already known to the investigators (i.e., patients of the Duke University Medical Center), a release of protected health information will be signed by the potential subjects to obtain records that can be used to confirm diagnosis.

Baseline / Visit 1:

Study subjects will be instructed to come to the DUMC to review and sign the informed consent document. At that time, complete medical history and complete physical examination will be obtained. Blood and urine will be collected for laboratory assessments. Height, weight, and vital signs (blood pressure, pulse, respiration) will be collected.

A nutritional history and review of diet dairy collected three days prior to the visit will be reviewed by a study dietitian. The blood glucose monitoring log for the three days prior to the visit will also be reviewed the study dietitian and MD. Study staff will collect concomitant medications and adverse event collection will begin once dosing with UX007 is initiated. An ultrasound with elastography will be conducted at the DUMCs radiology department and reviewed and a report generated by a radiologist.

Safety Phone Contact:

Subjects will be called by study staff the day after they start the UX007 and again 4 weeks later to assess nutritional history, review of glucose diary, review of dosing compliance, and to obtain an updated weight. Study staff will also review adverse events (AE/SAE) and concomitant medications during these calls. If a subject experiences an AE/SAE they will be contacted every two weeks until the AE/SAE is resolved.

2, 4, and 6 Month/Early Termination Visits:

Same procedures will be conducted as at the baseline visit, with the exception of the ultrasound with elastography, which will only be collected again at the 6 Month/Early Termination Visit.

Post-termination Phone Contact:

2-6 weeks after the 6 month/early termination visit study staff will contact the subject to collect an interim medical history, evaluation of nutritional history, review of glucose diary as well as review of adverse events and concomitant medications. An updated weight will also be obtained.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 5 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: This study is an interventional, open-label, feasibility pilot project to study the safety, efficacy, and tolerability of triheptanoin in patients with GSD I.
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Anaplerotic Therapy Using Triheptanoin for Patients With Glycogen Storage Disease Type I
Estimated Study Start Date : August 2020
Estimated Primary Completion Date : September 30, 2021
Estimated Study Completion Date : November 30, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Triheptanoin
Open Label Study
Drug: Triheptanoin
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.
Other Name: UX007




Primary Outcome Measures :
  1. Blood glucose level [ Time Frame: Baseline and 6 months ]
    Reviewing the change in blood glucose levels from baseline to 6 month visit


Secondary Outcome Measures :
  1. Dietary intake [ Time Frame: Baseline and 6 months ]
    Reviewing the change in fat, protein, and carbohydrate intake, after adding the intervention, from baseline to 6 month visit

  2. Liver steatosis assessment [ Time Frame: Baseline and 6 months ]
    Reviewing the change fatty infiltration (steatosis) using ultrasound elastography from baseline to 6 months visit. This technique will the degree of steatosis which is reflected by echogenicity and stiffness that is measured by 2D ultrasound shear wave speed measurements.

  3. Liver size assessment [ Time Frame: Baseline and 6 months ]
    Reviewing the change in liver size using ultrasound elastography from baseline to 6 months visit. This technique will provide liver size at both timepoints.

  4. Laboratory metabolic control markers [ Time Frame: Baseline and 6 months ]
    Reviewing laboratory markers indicative of metabolic control which include glucose, triglycerides, and uric acid measured in mg/dl from baseline to 6 month visit

  5. Other laboratory metabolic control markers [ Time Frame: Baseline and 6 months ]
    Reviewing lactate levels as a main indicator of metabolic control measured in mMol/L from baseline to 6 month visit



Information from the National Library of Medicine

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Ages Eligible for Study:   1 Month to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03665636


Contacts
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Contact: Jessica A Hester 919 668 3107 jessica.mcclain.jacobson@duke.edu
Contact: Stephanie Austin 919 668 1347 stephanie.austin@duke.edu

Locations
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United States, North Carolina
Duke University Medical Center Recruiting
Durham, North Carolina, United States, 27710
Contact: Jessica A Hester    919-668-3107    jessica.mcclain.jacobson@duke.edu   
Contact: Stephanie Austin    919 668 1347    stephanie.austin@duke.edu   
Principal Investigator: Areeg El-Gharbawy, MD         
Sponsors and Collaborators
Areeg El-Gharbawy
Ultragenyx Pharmaceutical Inc
Investigators
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Principal Investigator: Areeg El-Gharbawy, MD Duke University, Department of Pediatrics - Medical Genetics
Publications:

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Responsible Party: Areeg El-Gharbawy, Assistant Professor of Pediatrics, Duke University
ClinicalTrials.gov Identifier: NCT03665636    
Other Study ID Numbers: Pro00103582
First Posted: September 11, 2018    Key Record Dates
Last Update Posted: May 5, 2020
Last Verified: May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Areeg El-Gharbawy, Duke University:
Glycogen Storage Disease Type I
GSD I
Anaplerosis
Triheptanoin
Hypoglycemia
Additional relevant MeSH terms:
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Glycogen Storage Disease
Glycogen Storage Disease Type I
Metabolic Diseases
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn