Citrate Transporter DeficiencyNCT02500082
Triheptanoin (UX007) to Treat Citrate Transporter Deficiency
A study testing triheptanoin in people with Citrate Transporter Deficiency and SLC13A5 Gene Mutation, run by Irina A Anselm at 1 site in United States.
Trial summary
The purpose of this study is to determine whether triheptanoin (UX007) is effective in the treatment of neurological symptoms related to citrate transporter deficiency (SLC13A5 gene mutation). Read more about this study
- Who is it for?
- Ages 4 to 9 years
- Conditions the study is for
- Citrate Transporter Deficiency, SLC13A5 Gene Mutation
- What is being tested?
- triheptanoin
- Type of treatment
- Pill or oral medicine
- How many people
- Not given
- Where
- 1 siteUnited States
- Study dates
- Start not givento not given
- Phase
- Expanded access
- 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 4 to 9 years
- All sexes
- Child
Who may be able to join
- Diagnosis of citrate transporter deficiency due to mutations in the SLC13A5 gene.
- Presentation with severe global developmental delay and seizures.
Who cannot join
- Valproate is an AED that partially inhibits the TCA cycle via alpha-ketoglutarate dehydrogenase and should not be administered to subjects taking UX007.
Trial locations and contacts
1 site in 1 country.
United States1 site
Department of Neurology, Boston Children's Hospital
Boston, Massachusetts, 02115
About this study
Official title: Compassionate Use of Triheptanoin (UX007) to Treat Citrate Transporter Deficiency
The purpose of this study is to determine whether triheptanoin (UX007) is effective in the treatment of neurological symptoms related to citrate transporter deficiency (SLC13A5 gene mutation).
Read the detailed description
This compassionate use research study has been developed to study an investigational drug, triheptanoin (UX007), for the treatment of neurological symptoms related to citrate transporter deficiency, a disease with no existing treatment. The hypothesis is that triheptanoin will restore deficient energy metabolism in these patients, leading to improved seizure control, mental clarity, and physical strength.
Based on the literature, the SLC13A5 gene product is a citrate transporter. However, there is the possibility that other compounds are transported as well. The gene may be expressed in human neurons and function at the level of the plasma membrane. The hypothesis is that the transport of citrate across the plasma membrane from the extracellular space into the cytoplasm plays a role in maintaining the pool size of citrate in both the cytoplasm and mitochondrial matrix. Triheptanoin therapy may increase the metabolism of odd-chain fatty acids in neuronal mitochondria and thereby increase the levels of succinyl-CoA, leading to an increase in citrate concentrations. The increased level of citrate in the mitochondrial matrix may lead to an increased efflux of citrate from the matrix to the cytoplasm, thus increasing the cytoplasmic pool of citrate and allowing the malfunctioning citrate transporter to be bypassed. If successful, triheptanoin treatment will improve neuronal function and lead to an improvement in CNS function for patients.
While investigators will follow the course of subjects with considerable interest and may use some of the collected data for clinical research, this study is done for humanitarian reasons.
- Being tested
- triheptanoin
- Keywords
- citrate transporter deficiency, SLC13A5 gene, citric acid cycle, energy metabolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
triheptanoinDrug
Also called UX007
Triheptanoin (UX007) is a medium chain triglyceride of three seven-carbon fatty acids (C7), on a glycerol backbone, with a molecular formula of C24H44O6. It is being evaluated as a substrate replacement therapy for the treatment of long-chain fatty acid oxidation disorders (LC-FAOD) and for the treatment of seizures associated with Glut 1 DS. Triheptanoin is metabolized to provide substrate replacement for both fatty acid metabolism and anaplerosis (replacement of TCA cycle intermediates) required to restore the efficient generation of energy and the net production of glucose in patients. The mechanism of action of triheptanoin in restoring energy metabolism is dependent on its medium-chain length as well as its odd-carbon properties. Triheptanoin is a highly purified form intended for oral administration.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jul 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Citrate Transporter DeficiencyStudies 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
- Expanded access
Sponsor and investigators
- Lead sponsor
- Irina A Anselm
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Irina A Anselm, Boston Children's Hospital
- Investigators
- Irina A Anselm, MD, Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02500082
- Sponsor's protocol ID
- IRB-P00017250
- Status last verified
- Jan 2016
- First submitted
- 14 Jul 2015
- Last updated
- 28 Jan 2016
- Results posted
- No
Publications
Johannessen CU, Petersen D, Fonnum F, Hassel B. The acute effect of valproate on cerebral energy metabolism in mice. Epilepsy Res. 2001 Dec;47(3):247-56. doi: 10.1016/s0920-1211(01)00308-4.
PubMed 11738932Pascual JM, Liu P, Mao D, Kelly DI, Hernandez A, Sheng M, Good LB, Ma Q, Marin-Valencia I, Zhang X, Park JY, Hynan LS, Stavinoha P, Roe CR, Lu H. Triheptanoin for glucose transporter type I deficiency (G1D): modulation of human ictogenesis, cerebral metabolic rate, and cognitive indices by a food supplement. JAMA Neurol. 2014 Oct;71(10):1255-65. doi: 10.1001/jamaneurol.2014.1584.
PubMed 25110966Thevenon J, Milh M, Feillet F, St-Onge J, Duffourd Y, Juge C, Roubertie A, Heron D, Mignot C, Raffo E, Isidor B, Wahlen S, Sanlaville D, Villeneuve N, Darmency-Stamboul V, Toutain A, Lefebvre M, Chouchane M, Huet F, Lafon A, de Saint Martin A, Lesca G, El Chehadeh S, Thauvin-Robinet C, Masurel-Paulet A, Odent S, Villard L, Philippe C, Faivre L, Riviere JB. Mutations in SLC13A5 cause autosomal-recessive epileptic encephalopathy with seizure onset in the first days of life. Am J Hum Genet. 2014 Jul 3;95(1):113-20. doi: 10.1016/j.ajhg.2014.06.006.
PubMed 24995870
Study at a glance
From the registry record, last updated by the sponsor on 28 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Compassionate Use of Triheptanoin (UX007) to Treat Citrate Transporter Deficiency
- ClinicalTrials.gov ID
- NCT02500082
- Acronym / sponsor ID
- IRB-P00017250
- Keywords
- citrate transporter deficiency, SLC13A5 gene, citric acid cycle, energy metabolism
- Study type
- Expanded access
- Recruitment status
- No Longer Available
- Lead sponsor
- Irina A AnselmUniversity, hospital or other
- First posted
- 16 Jul 2015 (estimated)
- 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.
The purpose of this study is to determine whether triheptanoin (UX007) is effective in the treatment of neurological symptoms related to citrate transporter deficiency (SLC13A5 gene mutation).
Detailed description
This compassionate use research study has been developed to study an investigational drug, triheptanoin (UX007), for the treatment of neurological symptoms related to citrate transporter deficiency, a disease with no existing treatment. The hypothesis is that triheptanoin will restore deficient energy metabolism in these patients, leading to improved seizure control, mental clarity, and physical strength.
Based on the literature, the SLC13A5 gene product is a citrate transporter. However, there is the possibility that other compounds are transported as well. The gene may be expressed in human neurons and function at the level of the plasma membrane. The hypothesis is that the transport of citrate across the plasma membrane from the extracellular space into the cytoplasm plays a role in maintaining the pool size of citrate in both the cytoplasm and mitochondrial matrix. Triheptanoin therapy may increase the metabolism of odd-chain fatty acids in neuronal mitochondria and thereby increase the levels of succinyl-CoA, leading to an increase in citrate concentrations. The increased level of citrate in the mitochondrial matrix may lead to an increased efflux of citrate from the matrix to the cytoplasm, thus increasing the cytoplasmic pool of citrate and allowing the malfunctioning citrate transporter to be bypassed. If successful, triheptanoin treatment will improve neuronal function and lead to an improvement in CNS function for patients.
While investigators will follow the course of subjects with considerable interest and may use some of the collected data for clinical research, this study is done for humanitarian reasons.
Study design
Who may qualify
- Ages
- 4 to 9 years
- Sex
- All
- Age groups
- Child
Key inclusion criteria (2 listed)
- Diagnosis of citrate transporter deficiency due to mutations in the SLC13A5 gene.
- Presentation with severe global developmental delay and seizures.
Key exclusion criteria (1 listed)
- Valproate is an AED that partially inhibits the TCA cycle via alpha-ketoglutarate dehydrogenase and should not be administered to subjects taking UX007.
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: UX007Triheptanoin (UX007) is a medium chain triglyceride of three seven-carbon fatty acids (C7), on a glycerol backbone, with a molecular formula of C24H44O6. It is being evaluated as a substrate replacement therapy for the treatment of long-chain fatty acid oxidation disorders (LC-FAOD) and for the treatment of seizures associated with Glut 1 DS. Triheptanoin is metabolized to provide substrate replacement for both fatty acid metabolism and anaplerosis (replacement of TCA cycle intermediates) required to restore the efficient generation of energy and the net production of glucose in patients. The mechanism of action of triheptanoin in restoring energy metabolism is dependent on its medium-chain length as well as its odd-carbon properties. Triheptanoin is a highly purified form intended for oral administration. | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jan 2016.
- Background: PubMed 11738932Johannessen CU, Petersen D, Fonnum F, Hassel B. The acute effect of valproate on cerebral energy metabolism in mice. Epilepsy Res. 2001 Dec;47(3):247-56. doi: 10.1016/s0920-1211(01)00308-4.
- Background: PubMed 25110966Pascual JM, Liu P, Mao D, Kelly DI, Hernandez A, Sheng M, Good LB, Ma Q, Marin-Valencia I, Zhang X, Park JY, Hynan LS, Stavinoha P, Roe CR, Lu H. Triheptanoin for glucose transporter type I deficiency (G1D): modulation of human ictogenesis, cerebral metabolic rate, and cognitive indices by a food supplement. JAMA Neurol. 2014 Oct;71(10):1255-65. doi: 10.1001/jamaneurol.2014.1584.
- Background: PubMed 24995870Thevenon J, Milh M, Feillet F, St-Onge J, Duffourd Y, Juge C, Roubertie A, Heron D, Mignot C, Raffo E, Isidor B, Wahlen S, Sanlaville D, Villeneuve N, Darmency-Stamboul V, Toutain A, Lefebvre M, Chouchane M, Huet F, Lafon A, de Saint Martin A, Lesca G, El Chehadeh S, Thauvin-Robinet C, Masurel-Paulet A, Odent S, Villard L, Philippe C, Faivre L, Riviere JB. Mutations in SLC13A5 cause autosomal-recessive epileptic encephalopathy with seizure onset in the first days of life. Am J Hum Genet. 2014 Jul 3;95(1):113-20. doi: 10.1016/j.ajhg.2014.06.006.
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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.
Irina A Anselm, MD principal investigator
Boston Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing triheptanoin in people with Citrate Transporter Deficiency and SLC13A5 Gene Mutation, run by Irina A Anselm 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 2 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 28 Jan 2016. 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.
Are results available for this study?
Results are not available in the source record.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02500082, which also lists 3 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 28 Jan 2016.