An interventional study of Vitamin E in Hyperinsulinism-Hyperammonemia Syndrome, sponsored by Elizabeth A Rosenfeld. Completed at 1 site in United States. Open to participants aged 1 Year to 40 Years. Per ClinicalTrials.gov, last updated 2022-11-25.
Sponsored by Elizabeth A Rosenfeld · Not applicable, Interventional, and Other
Investigators will assess the tolerability of oral Vitamin E supplementation in subjects with congenital hyperinsulinism (HI) and hyperammonemia (HA) 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. Preliminary data show that Vitamin E (alpha-tocopherol) inhibits GDH activity in cell lines and improves hypoglycemia in a GDH HI mouse model. Based on these preclinical studies, Investigators hypothesize that Vitamin E will inhibit GDH activity and may impact hyperinsulinemic hypoglycemia and hyperammonemia in subjects with HI/HA syndrome. This hypothesis will be tested in a future study. In this initial pilot study, investigators will assess the tolerability of oral Vitamin E supplementation in subjects with HI/HA syndrome.
112 studies on the registry are indexed under Hyperinsulinism; 24 are open to participants now.
This study's enrollment of 14 is below the median of 29 across 79 interventional studies indexed under Hyperinsulinism.
Browse Hyperinsulinism studies →This is the only study on the registry with Elizabeth A Rosenfeld as lead sponsor.
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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.
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CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
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A drug or device being studied in a clinical trial.
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Contraception
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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.
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.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
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.
Daily oral supplementation with Vitamin E (alpha-tocopherol) for 2 weeks.
Dietary Supplement: Vitamin E
Subjects will take an oral Vitamin E (alpha-tocopherol) supplement once daily with a fat-containing meal for 2 weeks. The dose will be based on subject age (150 IU if 1-3 years old, 300 IU if 4-8 years old, 450 IU if 9-17 years old, 600 IU if \>17 years old). Formulations include 50 IU/mL liquid and 200 IU capsules. The liquid formulation will be used for subjects who will receive \<600 IU daily, or for any subjects who prefer liquid medication to capsules.
Also known as: alpha-tocopherol
Tolerability of Vitamin E Based on Responses to a Subject/Parent-reported Symptom Questionnaire After Vitamin E Supplementation Compared to Baseline
The following symptoms will be scored as either "none" (did not occur)=0, "mild" (minimal symptoms, no treatment needed)=1, "moderate" (symptoms requiring treatment at home or as an outpatient=2, or "severe" (symptoms requiring hospitalization or emergency room visit, or life-threatening or potentially life-threatening symptoms)=4: Seizure, Headache, Vision change/blurred vision, Weakness, Fatigue, Nausea, Vomiting, Diarrhea, Stomach pain, Constipation, Bruising, Bleeding, Rash, Itching, Other Symptom scores will be summed to yield a Tolerability Questionnaire Score for each participant. The Tolerability Questionnaire Score has a minimum score of 0 (symptoms did not occur) and a maximum score of 60 (all of the measured symptoms occurred, each with severe designation). The number (count) of participants with an increase in Tolerability Questionnaire Score from baseline to 2 weeks (following Vitamin E supplementation) will be reported.
Time frame: 2 weeks
Plasma Alpha-tocopherol Concentration
change in fasting plasma alpha-tocopherol concentration following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])
Time frame: 2 weeks
Delta-plasma Glucose Concentration
change in delta-glucose concentration (fasting plasma glucose - nadir plasma glucose during oral protein tolerance test) following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])
Time frame: 2 weeks
Fasting Plasma Glucose Concentration
change in fasting plasma glucose concentration following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])
Time frame: 2 weeks
Nadir Plasma Glucose Concentration
change in nadir plasma glucose concentration during oral protein tolerance test following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])
Time frame: 2 weeks
Fasting Plasma Insulin Concentration
change in fasting plasma insulin concentration following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])
Time frame: 2 weeks
Peak Plasma Insulin Concentration
change in peak plasma insulin concentration during oral protein tolerance test following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])
Time frame: 2 weeks
Delta-plasma Insulin Concentration
change in delta-plasma insulin concentration (peak plasma insulin - fasting plasma insulin during oral protein tolerance test) following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])
Time frame: 2 weeks
Fasting Plasma Ammonia Concentration
change in fasting plasma ammonia concentration following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])
Time frame: 2 weeks
Delta-plasma Ammonia Concentration
change in delta-plasma ammonia concentration (plasma ammonia at 60 minutes - fasting plasma ammonia during oral protein tolerance test) following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])
Time frame: 2 weeks
Hypoglycemia Frequency
change in frequency of hypoglycemia (plasma glucose \<70 mg/dL) detected on home glucose meter following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])
Time frame: 2 weeks
| Milestone | Vitamin E Supplementation |
|---|---|
| Started | 14 |
| Completed | 13 |
| Not completed | 1 |
| Withdrew: Withdrawal by subject | 1 |
The following symptoms will be scored as either "none" (did not occur)=0, "mild" (minimal symptoms, no treatment needed)=1, "moderate" (symptoms requiring treatment at home or as an outpatient=2, or "severe" (symptoms requiring hospitalization or emergency room visit, or life-threatening or potentially life-threatening symptoms)=4: Seizure, Headache, Vision change/blurred vision, Weakness, Fatigue, Nausea, Vomiting, Diarrhea, Stomach pain, Constipation, Bruising, Bleeding, Rash, Itching, Other Symptom scores will be summed to yield a Tolerability Questionnaire Score for each participant. The Tolerability Questionnaire Score has a minimum score of 0 (symptoms did not occur) and a maximum score of 60 (all of the measured symptoms occurred, each with severe designation). The number (count) of participants with an increase in Tolerability Questionnaire Score from baseline to 2 weeks (following Vitamin E supplementation) will be reported.
| Participants | Vitamin E Supplementation |
|---|---|
| Tolerability of Vitamin E Based on Responses to a Subject/Parent-reported Symptom Questionnaire After Vitamin E Supplementation Compared to Baseline | 2 |
change in fasting plasma alpha-tocopherol concentration following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])
| micromolar | Vitamin E Supplementation |
|---|---|
| Plasma Alpha-tocopherol Concentration | 18.6 ± 12.5 |
change in delta-glucose concentration (fasting plasma glucose - nadir plasma glucose during oral protein tolerance test) following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])
| mg/dL | Vitamin E Supplementation |
|---|---|
| Delta-plasma Glucose Concentration | 1.1 ± 8.3 |
change in fasting plasma glucose concentration following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])
| mg/dL | Vitamin E Supplementation |
|---|---|
| Fasting Plasma Glucose Concentration | -0.3 ± 6.5 |
change in nadir plasma glucose concentration during oral protein tolerance test following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])
| mg/dL | Vitamin E Supplementation |
|---|---|
| Nadir Plasma Glucose Concentration | 0.01 ± 9.46 |
change in fasting plasma insulin concentration following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])
| uIU/mL | Vitamin E Supplementation |
|---|---|
| Fasting Plasma Insulin Concentration | -2.4 ± 4.4 |
change in peak plasma insulin concentration during oral protein tolerance test following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])
| uIU/mL | Vitamin E Supplementation |
|---|---|
| Peak Plasma Insulin Concentration | -6.3 ± 18.2 |
change in delta-plasma insulin concentration (peak plasma insulin - fasting plasma insulin during oral protein tolerance test) following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])
| uIU/mL | Vitamin E Supplementation |
|---|---|
| Delta-plasma Insulin Concentration | -5.2 ± 16.5 |
change in fasting plasma ammonia concentration following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])
| micromolar | Vitamin E Supplementation |
|---|---|
| Fasting Plasma Ammonia Concentration | 1.0 ± 31.6 |
change in delta-plasma ammonia concentration (plasma ammonia at 60 minutes - fasting plasma ammonia during oral protein tolerance test) following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])
| micromolar | Vitamin E Supplementation |
|---|---|
| Delta-plasma Ammonia Concentration | -3.4 ± 15.5 |
change in frequency of hypoglycemia (plasma glucose \<70 mg/dL) detected on home glucose meter following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])
| Hypoglycemia events | Vitamin E Supplementation |
|---|---|
| Hypoglycemia Frequency | 0.6 ± 2.3 |
Collected over Adverse event data were collected over the 2 week study period.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Vitamin E Supplementation (All Doses) | 0/14 (0%) | 0/14 (0%) | 9/14 (64.3%) |
| Vitamin E 150 IU | 0/2 (0%) | 0/2 (0%) | 1/2 (50%) |
| Vitamin E 300 IU | 0/5 (0%) | 0/5 (0%) | 2/5 (40%) |
| Vitamin E 450 IU | 0/3 (0%) | 0/3 (0%) | 3/3 (100%) |
| Vitamin E 600 IU | 0/4 (0%) | 0/4 (0%) | 3/4 (75%) |
| Event | Vitamin E Supplementation (All Doses) | Vitamin E 150 IU | Vitamin E 300 IU | Vitamin E 450 IU | Vitamin E 600 IU |
|---|---|---|---|---|---|
| HeadacheNervous system disorders | 5/14 | 0/2 | 0/5 | 2/3 | 3/4 |
| VomitingGastrointestinal disorders | 4/14 | 1/2 | 0/5 | 2/3 | 1/4 |
| Abdominal painGastrointestinal disorders | 2/14 | 0/2 | 0/5 | 2/3 | 0/4 |
| Increased menstrual bleedingReproductive system and breast disorders | 1/14 | — | — | 0/2 | 1/3 |
| DiarrheaGastrointestinal disorders | 2/14 | 0/2 | 1/5 | 1/3 | 0/4 |
| FatigueGeneral disorders | 1/14 | 0/2 | 0/5 | 1/3 | 0/4 |
| Otitis externaInfections and infestations | 1/14 | 0/2 | 0/5 | 0/3 | 1/4 |
| RashSkin and subcutaneous tissue disorders | 1/14 | 0/2 | 1/5 | 0/3 | 0/4 |
| Age, Continuous(years) | Vitamin E Supplementation |
|---|---|
| Median | 8 (2 to 28) |
| Sex: Female, Male(Participants) | Vitamin E Supplementation |
|---|---|
| Female | 9 |
| Male | 5 |
| Ethnicity (NIH/OMB)(Participants) | Vitamin E Supplementation |
|---|---|
| Hispanic or Latino | 1 |
| Not Hispanic or Latino | 12 |
| Unknown or Not Reported | 1 |
| Race (NIH/OMB)(Participants) | Vitamin E Supplementation |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 5 |
| White | 6 |
| More than one race | 0 |
| Unknown or Not Reported | 2 |
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: No
Ran from Apr 2019 to primary completion in Mar 2020, 11 months.
Results were first posted in Nov 2022, 2 years 8 months after primary completion.
Of 24 interventional studies with no phase under Hyperinsulinism, half reached primary completion within 23 months of starting (the median), counting those still running; a quarter within 13 and three quarters within 90. This study's 11 months is below that.
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Studies of the drug tested here: Vitamin E