Glycogen Storage Disease Type IEarly Phase 1NCT03665636
Anaplerotic Therapy Using Triheptanoin for Patients With Glycogen Storage Disease Type I
A Early Phase 1 study testing Triheptanoin in people with Glycogen Storage Disease Type I, run by Areeg El-Gharbawy at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 month to 65 years
- Conditions the study is for
- Glycogen Storage Disease Type I
- What is being tested?
- Triheptanoin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Oct 2020to 21 Oct 2021
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 65 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Duke University Medical Center
Durham, North Carolina, 27710
About this study
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.
Read the 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.
- Conditions
- Glycogen Storage Disease Type I
- Being tested
- Triheptanoin
- Keywords
- Glycogen Storage Disease Type I, GSD I, Anaplerosis, Triheptanoin, Hypoglycemia
- Medical subject headings
- Glycogen Storage Disease Type I, Hypoglycemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TriheptanoinDrug
Also called UX007
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.
| Study group | Role | What they receive |
|---|---|---|
| Triheptanoin | Experimental | Open Label Study Receives: Drug: Triheptanoin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood glucose level
Reviewing the change in blood glucose levels from baseline to 6 month visit
Measured: Baseline and 6 months
Secondary outcomes (5)
Dietary intake
Reviewing the change in fat, protein, and carbohydrate intake, after adding the intervention, from baseline to 6 month visit
Measured: Baseline and 6 months
Liver steatosis assessment
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.
Measured: Baseline and 6 months
Liver size assessment
Reviewing the change in liver size using ultrasound elastography from baseline to 6 months visit. This technique will provide liver size at both timepoints.
Measured: Baseline and 6 months
Laboratory metabolic control markers
Reviewing laboratory markers indicative of metabolic control which include glucose, triglycerides, and uric acid measured in mg/dl from baseline to 6 month visit
Measured: Baseline and 6 months
Other laboratory metabolic control markers
Reviewing lactate levels as a main indicator of metabolic control measured in mMol/L from baseline to 6 month visit
Measured: Baseline and 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2018
- Study start16 Oct 2020
- Primary completion21 Oct 2021
- Study completion21 Oct 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Glycogen Storage Disease Type IStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- 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)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Areeg El-Gharbawy
- Sponsor type
- University, hospital or other
- Collaborators
- Ultragenyx Pharmaceutical Inc
- Responsible party
- Sponsor-investigator, Areeg El-Gharbawy, Duke University
- Investigators
- Areeg El-Gharbawy, MD, Principal investigator, Duke University, Department of Pediatrics - Medical Genetics
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03665636
- Sponsor's protocol ID
- Pro00103582
- Status last verified
- Dec 2021
- First submitted
- 23 Aug 2018
- Last updated
- 15 Dec 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 11949931Fernandes J, Pikaar NA. Ketosis in hepatic glycogenosis. Arch Dis Child. 1972 Feb;47(251):41-6. doi: 10.1136/adc.47.251.41.
PubMed 4336232Rasmussen 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.
PubMed 12464674Das 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.
PubMed 20357432Nagasaka 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.
PubMed 17206455Gu 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.
PubMed 19903863Farah 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.
PubMed 28317891Roe 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.
PubMed 16763896
Study at a glance
From the registry record, last updated by the sponsor on 15 Dec 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anaplerotic Therapy Using Triheptanoin for Patients With Glycogen Storage Disease Type I
- ClinicalTrials.gov ID
- NCT03665636
- Acronym / sponsor ID
- Pro00103582
- Conditions
- Glycogen Storage Disease Type I
- Keywords
- Glycogen Storage Disease Type I, GSD I, Anaplerosis, Triheptanoin, Hypoglycemia
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Areeg El-GharbawyUniversity, hospital or other
- Collaborators
- Ultragenyx Pharmaceutical Inc
- Study start
- 16 Oct 2020 (actual)
- Primary completion
- 21 Oct 2021 (actual)
- Study completion
- 21 Oct 2021 (actual)
- First posted
- 11 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| Triheptanoin | Experimental | Drug: TriheptanoinOpen Label Study |
Who may qualify
- Ages
- 1 month to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TriheptanoinAlso: UX007This 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. | Drug | Triheptanoin |
Primary outcome
Blood glucose level
Time frame: Baseline and 6 months
Reviewing the change in blood glucose levels from baseline to 6 month visit
5 secondary outcomes
Dietary intake
Time frame: Baseline and 6 months
Liver steatosis assessment
Time frame: Baseline and 6 months
Liver size assessment
Time frame: Baseline and 6 months
Laboratory metabolic control markers
Time frame: Baseline and 6 months
Other laboratory metabolic control markers
Time frame: Baseline and 6 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Dec 2021.
- Background: PubMed 11949931Chou 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.
- Background: PubMed 4336232Fernandes J, Pikaar NA. Ketosis in hepatic glycogenosis. Arch Dis Child. 1972 Feb;47(251):41-6. doi: 10.1136/adc.47.251.41.
- Background: PubMed 12464674Rasmussen 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.
- Background: PubMed 20357432Das 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.
- Background: PubMed 17206455Nagasaka 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.
- Background: PubMed 19903863Gu 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.
- Background: PubMed 28317891Farah 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.
- Background: PubMed 16763896Roe 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Areeg El-Gharbawy, MD principal investigator
Duke University, Department of Pediatrics - Medical Genetics
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Triheptanoin in people with Glycogen Storage Disease Type I, run by Areeg El-Gharbawy at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 15 Dec 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Blood glucose level (time frame: Baseline and 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03665636, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Dec 2021.