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

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ClinicalTrials.gov Identifier: NCT03665636
Recruitment Status : Not yet recruiting
First Posted : September 11, 2018
Last Update Posted : February 8, 2019
Sponsor:
Collaborator:
Ultragenyx Pharmaceutical Inc
Information provided by (Responsible Party):
Areeg El-Gharbawy, University of Pittsburgh

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 know to the investigators (i.e., patients of Medical Genetics at CHP), 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 UPMC Children's Hospital of Pittsburgh (CHP) 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 in CHP's 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
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 : April 2019
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : June 2020

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: Angela Leshinski, MBA, RD, LDN 412-692-5232 angela.leshinski@chp.edu
Contact: Elizabeth McCracken, MS, LCGC 412-692-5662 elizabeth.mccracken@chp.edu

Locations
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United States, Pennsylvania
UPMC Children's Hospital of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15210
Contact: Angela Leshinski, MBA, RD, LDN    412-692-5232    angela.leshinski@chp.edu   
Contact: Elizabeth McCracken, MS, LCGC    412-692-5662    elizabeth.mccracken@chp.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 University of Pittsburgh, UPMC Children's Hospital of Pittsburgh

Publications:

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Responsible Party: Areeg El-Gharbawy, Assistant Professor, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT03665636     History of Changes
Other Study ID Numbers: PRO17090545
First Posted: September 11, 2018    Key Record Dates
Last Update Posted: February 8, 2019
Last Verified: February 2019
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, University of Pittsburgh:
Glycogen Storage Disease Type I
GSD I
Anaplerosis
Triheptanoin
Hypoglycemia

Additional relevant MeSH terms:
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Metabolic Diseases
Glycogen Storage Disease
Glycogen Storage Disease Type I
Carbohydrate Metabolism, Inborn Errors
Metabolism, Inborn Errors
Genetic Diseases, Inborn