A Phase 2 interventional study of Vitamin E in Hyperinsulinism-Hyperammonemia Syndrome, sponsored by Children's Hospital of Philadelphia. Withdrawn at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-12-13.
Sponsored by Children's Hospital of Philadelphia · Phase 2, Interventional, and Treatment
Among 294 studies in Hypoglycemia with a site in United States — 36 open to participants now, 49 under way, 5 of them phase 3. Hypoglycemia · United States.
Among the 294 studies in Hypoglycemia with a site in United States, this one is the 228th largest by enrollment of the 239 interventional ones that give a count, is one of 12 that started in 2022, is one of 38 in phase 2, and was the 228th registered.
706 studies on the registry are indexed under Hypoglycemia; 94 are open to participants now.
Browse Hypoglycemia studies →36 of the 294 studies in Hypoglycemia with a site in United States are open now. Recruiting first, the newest first:
Vogenx, Inc. · Sites in United States
Ages 18+
Indiana University · Sites in United States
Ages 65+
Indiana University · Sites in United States
Ages 7–25
Joslin Diabetes Center · Sites in United States
Ages 18–70 · Healthy volunteers
Indiana University · Sites in United States
Ages 12–19
A study can be open while its sites in United States have not opened yet or have stopped. Only those recruiting at a site in United States →
Of the 59 Hypoglycemia studies recruiting now, 23 (39%) set no upper age limit and 31 (53%) stop at 75 or younger; 18 take children under 18; 14 take healthy volunteers.
This study: 18 Years and older · all sexes · no healthy volunteers.
The full table on the hub →This tab as a report to print or save as PDF → With an account.
294 studies; the count open now beside each. This study's row is marked.
A study in two phases is counted once above. Listed by phase, each with its combined phases: Phase 1 54 · Phase 2 69 · Phase 3 35 · Phase 4 12
First in 1991; this study’s year is marked. 12 started in 2022.
By drug class, each counting the studies that test any of its medicines:
Median enrollment 24 across the 239 interventional studies, 71 across the 48 observational. Of the 219 that completed or were terminated, 102 (47%) have results posted.
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52 of 294 have an industry lead sponsor. The 10 most frequent:
Children's Hospital of Philadelphia is the lead sponsor of 489 studies on the registry; 90 are open to participants now.
Of its 28 completed or terminated interventional studies of FDA-regulated products, 22 (79%) have results posted.
Children's Hospital of Philadelphia has 2 studies filed under Hypoglycemia — fewer than ten, so there is no comparison to draw.
18 of the studies in Hypoglycemia with a site in United States that are under way reach primary completion within a year, 1 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT06881992Phase 3RezoluteA Phase 3 Study of Ersodetug in Patients With Tumor Hyperinsulinism | 2027-09 |
| NCT07215312Eli Lilly and CompanyA Study of LY3938577 in Participants With Type 2 Diabetes Previously Treated With Basal Insulin | 2026-11 |
| NCT04428723Joslin Diabetes CenterMechanisms of Hypoglycemia in Patients Without Diabetes | 2026-12 |
| NCT05762107Zucara Therapeutics Inc.A Study of the Effect of ZT-01 on Night-time Hypoglycemia in Type 1 Diabetes | 2026-12 |
| NCT06893341Indiana UniversityMonitoring Exhaled Breath to Noninvasively Detect Glycemic Events | 2026-12-01 |
Add all 18 to your calendar (.ics) → With an account.
Among the 294 studies in Hypoglycemia with a site in United States, from their registry updates:
This tab as a report to print or save as PDF → With an account.
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.
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.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
INR, PT and aPTT (clotting tests)
Blood tests of how long blood takes to clot. The INR is the prothrombin time (PT) put on a common scale; about 1 is usual for someone not taking a blood thinner.
Criteria often make an exception for people on a blood thinner such as warfarin, whose INR is raised on purpose.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
ULN (upper limit of normal)
The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.
“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hemoglobin (Hb)
The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Investigational drug or device
A drug or device being studied in a clinical trial.
It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Drug: Vitamin E
Twice daily oral supplementation with Vitamin E for 6-9 weeks.
Also known as: dl-alpha-tocopherol
protein-induced hyperinsulinemia
Change in plasma insulin concentration area under the curve (AUC) during leucine AIR test after vitamin E treatment compared to before.
Time frame: 4-11 weeks
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 4-11 weeks
vitamin E
Change in serum alpha-tocopherol concentration after vitamin E treatment compared to before.
Time frame: 4-11 weeks
ammonia
Change in blood ammonia concentration after vitamin E treatment compared to before.
Time frame: 4-11 weeks
seizures
Change in frequency of seizures, based on symptom questionnaire, after vitamin E treatment compared to before.
Time frame: 4-11 weeks
number of participants with EEG abnormalities
Change in brain electrical activity after vitamin E treatment compared to before.
Time frame: 8-11 weeks
brain glutamate
Change in glutamate concentration, as measured by brain GluCEST percent contrast, after vitamin E treatment compared to before.
Time frame: 8-11 weeks
Plan to share: No
Start is estimated for Nov 2022; primary completion for Mar 2023, 4 months later.
How these figures are worked out, and which studies are left out of them.
This study is withdrawn, as verified in Dec 2022. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Vitamin E
Children's Hospital of Philadelphia →