Hyperinsulinism-Hyperammonemia SyndromePhase 2NCT04984798
Vitamin E Efficacy in HI/HA
A Phase 2 study testing Vitamin E in people with Hyperinsulinism-Hyperammonemia Syndrome, run by Children's Hospital of Philadelphia at 1 site in United States.
Trial summary
Congenital hyperinsulinism (HI) is a rare disorder of pancreatic beta cell insulin secretion that causes persistent and severe hypoglycemia starting at birth. Hyperinsulinism/hyperammonemia (HI/HA) syndrome is the second most common type of congenital HI and is caused by activating mutations in glutamate dehydrogenase… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hyperinsulinism-Hyperammonemia Syndrome
- What is being tested?
- Vitamin E
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2022to Mar 2023
- Phase
- Phase 2
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females age ≥18 years.
- Diagnosis of HI/HA syndrome (based on glutamate dehydrogenase 1 [GLUD1] genetic test result and/or history of diazoxide-responsive hyperinsulinism with persistently elevated blood ammonia concentrations).
- Able to swallow softgels.
- Informed consent.
Who cannot join
- Vitamin E supplementation within 30 days prior to enrollment, including multivitamins containing vitamin E.
- Individuals who have experienced an allergic reaction to vitamin E.
- On concurrent therapy with a medication known to adversely interact with vitamin E.
- On concurrent therapy with a medication, supplement, or herbal remedy known to increase bleeding risk, including antiplatelet or anticoagulation therapy.
- Known increased risk of bleeding (coagulopathy, hemophilia, platelet defect, or platelet disorder) based on history, known or suspected vitamin K deficiency, baseline international normalized ratio (INR) >1.5, baseline prothrombin time (PT) >1.5 times the upper limit of normal, baseline partial thromboplastin time (PTT) >1.5 times the upper limit of normal, or baseline abnormal platelet function test result (VerifyNow-Aspirin <550 aspirin reactivity units [ARU], VerifyNow-adenosine diphosphate [ADP]/PRU <180 P2Y12 reaction units [PRU]).
- Known clotting disorder, including prior episodes of deep vein thrombosis or pulmonary embolism within the past 6 months.
Show all 17Show fewer
- Evidence of severe hematologic abnormality including severe anemia (Hgb <10 g/dL) and/or thrombocytopenia (platelet count <150,000/mm3).
- Abnormal score on International Society on Thrombosis and Haemostasis (ISTH)-Bleeding Assessment Tool (>4 if male; >5 if female).
- Planned elective surgical procedure during study period.
- Evidence of a medical condition that might alter results or compromise the interpretation of results, including active infection, kidney failure, severe liver dysfunction, severe respiratory or cardiac failure.
- Any investigational drug use within 30 days prior to enrollment.
- Current use of somatostatin analog.
- Current adherence to a ketogenic diet.
- Pregnant or lactating females. Females must have a negative urine pregnancy test and must use an acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), Depo-Provera, or an oral contraceptive, for the duration of the study and a minimum of 2 weeks after the last dose of study drug.
- Subjects who, in the opinion of the Investigator, may be non-compliant with study schedules or procedures.
- Unable to provide informed consent (e.g. impaired cognition or judgment).
- Limited English proficiency.
Trial locations and contacts
1 site in 1 country.
United States1 site
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
About this study
Official title: Efficacy of Vitamin E in Hyperinsulinism/Hyperammonemia Syndrome
Congenital hyperinsulinism (HI) is a rare disorder of pancreatic beta cell insulin secretion that causes persistent and severe hypoglycemia starting at birth. Hyperinsulinism/hyperammonemia (HI/HA) syndrome is the second most common type of congenital HI and is caused by activating mutations in glutamate dehydrogenase (GDH). Patients with HI/HA exhibit fasting hyperinsulinemic hypoglycemia, protein-induced hypoglycemia, hyperammonemia, seizures, and intellectual disability independent of hypoglycemia. These effects result from abnormal GDH activity in the beta cells, liver and kidney cells, neurons, and astrocytes. The only available treatment for HI/HA syndrome is diazoxide, which acts on the beta cells to decrease insulin secretion but has no effect on GDH activity itself or on other cell types. Thus, there remains a significant unmet need for improved therapies for this disorder. Pre-clinical data show that vitamin E inhibits GDH activity in human cell lines and improves fasting hypoglycemia in a GDH HI mouse model. Pilot study data show that vitamin E supplementation with a moderate dose is well-tolerated in children and adults with HI/HA syndrome, while continuing diazoxide treatment. However, most subjects continued to exhibit protein-induced hyperinsulinemic hypoglycemia. We hypothesize that a higher vitamin E dose will inhibit GDH over-activity in subjects with HI/HA syndrome, resulting in improved hyperinsulinemic hypoglycemia, reduced blood ammonia concentration, and decreased seizure activity.
Read the detailed description
The primary objective of this study is to determine an effective dose of vitamin E to reduce protein-induced hyperinsulinemia in subjects with HI/HA syndrome. Secondary objectives are to assess the effects of vitamin E on plasma C-peptide concentrations, serum alpha-tocopherol concentrations, blood ammonia concentrations, hypoglycemic events, and seizure frequency. The effect of vitamin E on brain glutamate levels and electroencephalogram findings will be explored.
This single-group open-label dose-finding clinical study will use a before-and-after design to compare clinical and laboratory data before and after 2-3 weeks of escalating doses of oral vitamin E treatment in subjects with HI/HA syndrome.
This single-site outpatient study will recruit up to 5 adult participants (18 years of age or older) with HI/HA syndrome.
Each study visit will consist of blood tests, an IV leucine acute insulin response (AIR) test, home glucose meter and continuous glucose monitor (CGM) review, and a symptom questionnaire. The baseline and final visits will also include electroencephalogram (EEG) and brain magnetic resonance imaging (MRI) with glutamate chemical exchange saturation transfer (GluCEST) analysis. After baseline assessments, including a 2 week run-in period of CGM use, subjects will take twice daily oral vitamin E (alpha-tocopherol) at home. After steady-state of that dose of vitamin E has been achieved (i.e. at least 2 weeks on the dose of vitamin E), subjects will return for the next study visit. If there is no dose-limiting toxicity, then the twice daily vitamin E dose will be increased, and the subjects will return for a subsequent study visit after at least 2 weeks. If there is no dose-limiting toxicity at this visit, then the twice daily vitamin E dose will be increased again, and the subjects will return for a final study visit after at least 2 weeks. If toxicity is identified at any point, vitamin E will be discontinued and final study visit procedures will be performed.
- Conditions
- Hyperinsulinism-Hyperammonemia Syndrome
- Being tested
- Vitamin E
- Keywords
- hypoglycemia, hyperinsulinism, vitamin E
- Medical subject headings
- Hyperinsulinemic hypoglycemia, familial, 6, Hypoglycemia, Hyperinsulinism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vitamin EDrug
Also called dl-alpha-tocopherol
Twice daily oral supplementation with Vitamin E for 6-9 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Vitamin E Dose-Escalation | Experimental | Subjects will take an oral Vitamin E (dl-alpha-tocopherol) supplement twice daily with a fat-containing meal for 6-9 weeks. The dose will be increased every 2-3 weeks over the course of the study (initial dose 600 IU twice daily, next dose 1,200 IU twice daily, final dose 2,400 IU twice daily). Formulations include softgel capsules in 200, 400, and 1,000 IU doses. Receives: Drug: Vitamin E |
What is being measured
The primary outcome is the main question the study is designed to answer.
protein-induced hyperinsulinemia
Change in plasma insulin concentration area under the curve (AUC) during leucine AIR test after vitamin E treatment compared to before.
Measured: 4-11 weeks
Secondary outcomes (8)
mean glucose concentration
Change in mean glucose concentration detected on continuous glucose monitor (CGM) during the study interval after vitamin E treatment compared to before.
Measured: 4-11 weeks
proportion of time spent with glucose <70 mg/dL
Change in proportion of time spent with glucose <70 mg/dL, detected on continuous glucose monitor (CGM) during the study interval after vitamin E treatment compared to before.
Measured: 4-11 weeks
proportion of time spent with glucose <50 mg/dL
Change in proportion of time spent with glucose <50 mg/dL, detected on continuous glucose monitor (CGM) during the study interval after vitamin E treatment compared to before.
Measured: 4-11 weeks
hypoglycemic episodes
Change in frequency of hypoglycemic episodes (plasma glucose <70 mg/dL and plasma glucose <50 mg/dL) detected on home glucose meter and/or continuous glucose monitor (CGM) after vitamin E treatment compared to before.
Measured: 4-11 weeks
protein-induced C-peptide release
Change in plasma C-peptide concentration area under the curve (AUC) during leucine AIR test after vitamin E treatment compared to before.
Measured: 4-11 weeks
vitamin E
Change in serum alpha-tocopherol concentration after vitamin E treatment compared to before.
Measured: 4-11 weeks
ammonia
Change in blood ammonia concentration after vitamin E treatment compared to before.
Measured: 4-11 weeks
seizures
Change in frequency of seizures, based on symptom questionnaire, after vitamin E treatment compared to before.
Measured: 4-11 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Aug 2021
- Study startNov 2022 (estimated)
- Primary completionMar 2023 (estimated)
- Study completionMar 2023 (estimated)
Why it stopped: No study activity took place. The IND was withdrawn with the FDA by the Sponsor Investigator because of insurmountable hurdles in moving proposed research forward
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 Hyperinsulinism-Hyperammonemia SyndromeStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This single-group open-label dose-finding clinical study will use a before-and-after design, with repeated outpatient evaluations.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Collaborators
- University of Pennsylvania, Lawson Wilkins Pediatric Endocrine Society
- Responsible party
- Principal investigator, Elizabeth A Rosenfeld, Children's Hospital of Philadelphia
- Investigators
- Elizabeth A Rosenfeld, MD, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04984798
- Sponsor's protocol ID
- 20-018039
- Status last verified
- Dec 2022
- First submitted
- 3 Dec 2020
- Last updated
- 13 Dec 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Palladino AA, Stanley CA. The hyperinsulinism/hyperammonemia syndrome. Rev Endocr Metab Disord. 2010 Sep;11(3):171-8. doi: 10.1007/s11154-010-9146-0.
PubMed 20936362Snider KE, Becker S, Boyajian L, Shyng SL, MacMullen C, Hughes N, Ganapathy K, Bhatti T, Stanley CA, Ganguly A. Genotype and phenotype correlations in 417 children with congenital hyperinsulinism. J Clin Endocrinol Metab. 2013 Feb;98(2):E355-63. doi: 10.1210/jc.2012-2169. Epub 2012 Dec 28.
PubMed 23275527Hsu BY, Kelly A, Thornton PS, Greenberg CR, Dilling LA, Stanley CA. Protein-sensitive and fasting hypoglycemia in children with the hyperinsulinism/hyperammonemia syndrome. J Pediatr. 2001 Mar;138(3):383-9. doi: 10.1067/mpd.2001.111818.
PubMed 11241047Kelly A, Ng D, Ferry RJ Jr, Grimberg A, Koo-McCoy S, Thornton PS, Stanley CA. Acute insulin responses to leucine in children with the hyperinsulinism/hyperammonemia syndrome. J Clin Endocrinol Metab. 2001 Aug;86(8):3724-8. doi: 10.1210/jcem.86.8.7755.
PubMed 11502802Stanley CA, Baker L. Hyperinsulinism in infancy: diagnosis by demonstration of abnormal response to fasting hypoglycemia. Pediatrics. 1976 May;57(5):702-11.
PubMed 940710Li M, Smith CJ, Walker MT, Smith TJ. Novel inhibitors complexed with glutamate dehydrogenase: allosteric regulation by control of protein dynamics. J Biol Chem. 2009 Aug 21;284(34):22988-3000. doi: 10.1074/jbc.M109.020222. Epub 2009 Jun 15.
PubMed 19531491Treberg JR, Clow KA, Greene KA, Brosnan ME, Brosnan JT. Systemic activation of glutamate dehydrogenase increases renal ammoniagenesis: implications for the hyperinsulinism/hyperammonemia syndrome. Am J Physiol Endocrinol Metab. 2010 Jun;298(6):E1219-25. doi: 10.1152/ajpendo.00028.2010. Epub 2010 Mar 23.
PubMed 20332361Ferslew KE, Acuff RV, Daigneault EA, Woolley TW, Stanton PE Jr. Pharmacokinetics and bioavailability of the RRR and all racemic stereoisomers of alpha-tocopherol in humans after single oral administration. J Clin Pharmacol. 1993 Jan;33(1):84-8. doi: 10.1002/j.1552-4604.1993.tb03909.x.
PubMed 8429120
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Vitamin E in Hyperinsulinism/Hyperammonemia Syndrome
- ClinicalTrials.gov ID
- NCT04984798
- Acronym / sponsor ID
- 20-018039
- Conditions
- Hyperinsulinism-Hyperammonemia Syndrome
- Keywords
- hypoglycemia, hyperinsulinism, vitamin E
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No study activity took place. The IND was withdrawn with the FDA by the Sponsor Investigator because of insurmountable hurdles in moving proposed research forward
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Collaborators
- University of Pennsylvania, Lawson Wilkins Pediatric Endocrine Society
- Study start
- Nov 2022 (estimated)
- Primary completion
- Mar 2023 (estimated)
- Study completion
- Mar 2023 (estimated)
- First posted
- 2 Aug 2021 (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.
Congenital hyperinsulinism (HI) is a rare disorder of pancreatic beta cell insulin secretion that causes persistent and severe hypoglycemia starting at birth. Hyperinsulinism/hyperammonemia (HI/HA) syndrome is the second most common type of congenital HI and is caused by activating mutations in glutamate dehydrogenase (GDH). Patients with HI/HA exhibit fasting hyperinsulinemic hypoglycemia, protein-induced hypoglycemia, hyperammonemia, seizures, and intellectual disability independent of hypoglycemia. These effects result from abnormal GDH activity in the beta cells, liver and kidney cells, neurons, and astrocytes. The only available treatment for HI/HA syndrome is diazoxide, which acts on the beta cells to decrease insulin secretion but has no effect on GDH activity itself or on other cell types. Thus, there remains a significant unmet need for improved therapies for this disorder. Pre-clinical data show that vitamin E inhibits GDH activity in human cell lines and improves fasting hypoglycemia in a GDH HI mouse model. Pilot study data show that vitamin E supplementation with a moderate dose is well-tolerated in children and adults with HI/HA syndrome, while continuing diazoxide treatment. However, most subjects continued to exhibit protein-induced hyperinsulinemic hypoglycemia. We hypothesize that a higher vitamin E dose will inhibit GDH over-activity in subjects with HI/HA syndrome, resulting in improved hyperinsulinemic hypoglycemia, reduced blood ammonia concentration, and decreased seizure activity.
Detailed description
The primary objective of this study is to determine an effective dose of vitamin E to reduce protein-induced hyperinsulinemia in subjects with HI/HA syndrome. Secondary objectives are to assess the effects of vitamin E on plasma C-peptide concentrations, serum alpha-tocopherol concentrations, blood ammonia concentrations, hypoglycemic events, and seizure frequency. The effect of vitamin E on brain glutamate levels and electroencephalogram findings will be explored.
This single-group open-label dose-finding clinical study will use a before-and-after design to compare clinical and laboratory data before and after 2-3 weeks of escalating doses of oral vitamin E treatment in subjects with HI/HA syndrome.
This single-site outpatient study will recruit up to 5 adult participants (18 years of age or older) with HI/HA syndrome.
Each study visit will consist of blood tests, an IV leucine acute insulin response (AIR) test, home glucose meter and continuous glucose monitor (CGM) review, and a symptom questionnaire. The baseline and final visits will also include electroencephalogram (EEG) and brain magnetic resonance imaging (MRI) with glutamate chemical exchange saturation transfer (GluCEST) analysis. After baseline assessments, including a 2 week run-in period of CGM use, subjects will take twice daily oral vitamin E (alpha-tocopherol) at home. After steady-state of that dose of vitamin E has been achieved (i.e. at least 2 weeks on the dose of vitamin E), subjects will return for the next study visit. If there is no dose-limiting toxicity, then the twice daily vitamin E dose will be increased, and the subjects will return for a subsequent study visit after at least 2 weeks. If there is no dose-limiting toxicity at this visit, then the twice daily vitamin E dose will be increased again, and the subjects will return for a final study visit after at least 2 weeks. If toxicity is identified at any point, vitamin E will be discontinued and final study visit procedures will be performed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This single-group open-label dose-finding clinical study will use a before-and-after design, with repeated outpatient evaluations.
| Arm | Type | Receives |
|---|---|---|
| Vitamin E Dose-Escalation | Experimental | Drug: Vitamin ESubjects will take an oral Vitamin E (dl-alpha-tocopherol) supplement twice daily with a fat-containing meal for 6-9 weeks. The dose will be increased every 2-3 weeks over the course of the study (initial dose 600 IU twice daily, next dose 1,200 IU twice daily, final dose 2,400 IU twice daily). Formulations include softgel capsules in 200, 400, and 1,000 IU doses. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Males or females age ≥18 years.
- Diagnosis of HI/HA syndrome (based on glutamate dehydrogenase 1 [GLUD1] genetic test result and/or history of diazoxide-responsive hyperinsulinism with persistently elevated blood ammonia concentrations).
- Able to swallow softgels.
- Informed consent.
Key exclusion criteria (17 listed)
- Vitamin E supplementation within 30 days prior to enrollment, including multivitamins containing vitamin E.
- Individuals who have experienced an allergic reaction to vitamin E.
- On concurrent therapy with a medication known to adversely interact with vitamin E.
- On concurrent therapy with a medication, supplement, or herbal remedy known to increase bleeding risk, including antiplatelet or anticoagulation therapy.
- Known increased risk of bleeding (coagulopathy, hemophilia, platelet defect, or platelet disorder) based on history, known or suspected vitamin K deficiency, baseline international normalized ratio (INR) >1.5, baseline prothrombin time (PT) >1.5 times the upper limit of normal, baseline partial thromboplastin time (PTT) >1.5 times the upper limit of normal, or baseline abnormal platelet function test result (VerifyNow-Aspirin <550 aspirin reactivity units [ARU], VerifyNow-adenosine diphosphate [ADP]/PRU <180 P2Y12 reaction units [PRU]).
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 |
|---|---|---|
| Vitamin EAlso: dl-alpha-tocopherolTwice daily oral supplementation with Vitamin E for 6-9 weeks. | Drug | Vitamin E Dose-Escalation |
Primary outcome
protein-induced hyperinsulinemia
Time frame: 4-11 weeks
Change in plasma insulin concentration area under the curve (AUC) during leucine AIR test after vitamin E treatment compared to before.
8 secondary outcomes
mean glucose concentration
Time frame: 4-11 weeks
proportion of time spent with glucose <70 mg/dL
Time frame: 4-11 weeks
proportion of time spent with glucose <50 mg/dL
Time frame: 4-11 weeks
hypoglycemic episodes
Time frame: 4-11 weeks
protein-induced C-peptide release
Time frame: 4-11 weeks
vitamin E
Time frame: 4-11 weeks
ammonia
Time frame: 4-11 weeks
seizures
Time frame: 4-11 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2022.
- Background: PubMed 20936362Palladino AA, Stanley CA. The hyperinsulinism/hyperammonemia syndrome. Rev Endocr Metab Disord. 2010 Sep;11(3):171-8. doi: 10.1007/s11154-010-9146-0.
- Background: PubMed 23275527Snider KE, Becker S, Boyajian L, Shyng SL, MacMullen C, Hughes N, Ganapathy K, Bhatti T, Stanley CA, Ganguly A. Genotype and phenotype correlations in 417 children with congenital hyperinsulinism. J Clin Endocrinol Metab. 2013 Feb;98(2):E355-63. doi: 10.1210/jc.2012-2169. Epub 2012 Dec 28.
- Background: PubMed 11241047Hsu BY, Kelly A, Thornton PS, Greenberg CR, Dilling LA, Stanley CA. Protein-sensitive and fasting hypoglycemia in children with the hyperinsulinism/hyperammonemia syndrome. J Pediatr. 2001 Mar;138(3):383-9. doi: 10.1067/mpd.2001.111818.
- Background: PubMed 11502802Kelly A, Ng D, Ferry RJ Jr, Grimberg A, Koo-McCoy S, Thornton PS, Stanley CA. Acute insulin responses to leucine in children with the hyperinsulinism/hyperammonemia syndrome. J Clin Endocrinol Metab. 2001 Aug;86(8):3724-8. doi: 10.1210/jcem.86.8.7755.
- Background: PubMed 940710Stanley CA, Baker L. Hyperinsulinism in infancy: diagnosis by demonstration of abnormal response to fasting hypoglycemia. Pediatrics. 1976 May;57(5):702-11.
- Background: PubMed 19531491Li M, Smith CJ, Walker MT, Smith TJ. Novel inhibitors complexed with glutamate dehydrogenase: allosteric regulation by control of protein dynamics. J Biol Chem. 2009 Aug 21;284(34):22988-3000. doi: 10.1074/jbc.M109.020222. Epub 2009 Jun 15.
- Background: PubMed 20332361Treberg JR, Clow KA, Greene KA, Brosnan ME, Brosnan JT. Systemic activation of glutamate dehydrogenase increases renal ammoniagenesis: implications for the hyperinsulinism/hyperammonemia syndrome. Am J Physiol Endocrinol Metab. 2010 Jun;298(6):E1219-25. doi: 10.1152/ajpendo.00028.2010. Epub 2010 Mar 23.
- Background: PubMed 8429120Ferslew KE, Acuff RV, Daigneault EA, Woolley TW, Stanton PE Jr. Pharmacokinetics and bioavailability of the RRR and all racemic stereoisomers of alpha-tocopherol in humans after single oral administration. J Clin Pharmacol. 1993 Jan;33(1):84-8. doi: 10.1002/j.1552-4604.1993.tb03909.x.
- Individual participant dataSharing planned: No
Related trials for Hyperinsulinism-Hyperammonemia Syndrome
Active, not recruitingObservational study
Early Check: Expanded Screening in Newborns
Spinal Muscular Atrophy, Fragile X Syndrome
Enrolling by invitationObservational study
International Registry of Congenital Portosystemic Shunt (IRCPSS)
Congenital Portosystemic Shunt, CPSS (Congenital Portosystemic Shunt)
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.
Elizabeth A Rosenfeld, MD principal investigator
Children's Hospital of Philadelphia
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Vitamin E in people with Hyperinsulinism-Hyperammonemia Syndrome, run by Children's Hospital of Philadelphia 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 4 inclusion and 17 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: withdrawn, as of the sponsor's last update on 13 Dec 2022. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 was withdrawn before enrolling participants, so there are no results.
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?
protein-induced hyperinsulinemia (time frame: 4-11 weeks). 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 NCT04984798, 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 13 Dec 2022.