Trial Outcomes & Findings for Vitamin E Supplementation in Hyperinsulinism/Hyperammonemia Syndrome (NCT NCT03797222)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

14 participants

Primary outcome timeframe

2 weeks

Results posted on

2022-11-25

Participant Flow

Participant milestones

Participant milestones
Measure	Vitamin E Supplementation Daily oral supplementation with Vitamin E (alpha-tocopherol) for 2 weeks. 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.
Overall Study STARTED	14
Overall Study COMPLETED	13
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Vitamin E Supplementation Daily oral supplementation with Vitamin E (alpha-tocopherol) for 2 weeks. 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.
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Vitamin E Supplementation in Hyperinsulinism/Hyperammonemia Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vitamin E Supplementation n=14 Participants Daily oral supplementation with Vitamin E (alpha-tocopherol) for 2 weeks. 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.
Age, Continuous	8 years n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants
Sex: Female, Male Male	5 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants
Race (NIH/OMB) White	6 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	2 Participants n=5 Participants

PRIMARY outcome

Timeframe: 2 weeks

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.

Outcome measures

Outcome measures
Measure	Vitamin E Supplementation n=13 Participants Daily oral supplementation with Vitamin E (alpha-tocopherol) for 2 weeks. 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.
Tolerability of Vitamin E Based on Responses to a Subject/Parent-reported Symptom Questionnaire After Vitamin E Supplementation Compared to Baseline	2 Participants

SECONDARY outcome

Timeframe: 2 weeks

Population: The 2 week (visit 2) laboratory draw was unable to be obtained for 1 participant, yielding n=12 analyzed for this outcome

change in fasting plasma alpha-tocopherol concentration following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])

Outcome measures

Outcome measures
Measure	Vitamin E Supplementation n=12 Participants Daily oral supplementation with Vitamin E (alpha-tocopherol) for 2 weeks. 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.
Plasma Alpha-tocopherol Concentration	18.6 micromolar Standard Deviation 12.5

SECONDARY outcome

Timeframe: 2 weeks

Population: Per the study protocol, the oral protein tolerance test was not repeated at 2 weeks (visit 2) if the baseline (visit 1) oral protein tolerance test was not tolerated. Of the 13 participants who completed the study, 7 did not tolerate the baseline (visit 1) oral protein tolerance test. The 2 week (visit 2) oral protein tolerance test was performed in 6 participants. Oral protein tolerance test parameters were analyzed for these 6 participants.

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 \[visit 1\])

Outcome measures

Outcome measures
Measure	Vitamin E Supplementation n=6 Participants Daily oral supplementation with Vitamin E (alpha-tocopherol) for 2 weeks. 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.
Delta-plasma Glucose Concentration	1.1 mg/dL Standard Deviation 8.3

SECONDARY outcome

Timeframe: 2 weeks

Population: The 2 week (visit 2) laboratory draw was unable to be obtained for 1 participant, yielding n=12 analyzed for this outcome

change in fasting plasma glucose concentration following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])

Outcome measures

Outcome measures
Measure	Vitamin E Supplementation n=12 Participants Daily oral supplementation with Vitamin E (alpha-tocopherol) for 2 weeks. 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.
Fasting Plasma Glucose Concentration	-0.3 mg/dL Standard Deviation 6.5

SECONDARY outcome

Timeframe: 2 weeks

Population: Per the study protocol, the oral protein tolerance test was not repeated at 2 weeks (visit 2) if the baseline (visit 1) oral protein tolerance test was not tolerated. Of the 13 participants who completed the study, 7 did not tolerate the baseline (visit 1) oral protein tolerance test. The 2 week (visit 2) oral protein tolerance test was performed in 6 participants. Oral protein tolerance test parameters were analyzed for these 6 participants.

change in nadir plasma glucose concentration during oral protein tolerance test following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])

Outcome measures

Outcome measures
Measure	Vitamin E Supplementation n=6 Participants Daily oral supplementation with Vitamin E (alpha-tocopherol) for 2 weeks. 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.
Nadir Plasma Glucose Concentration	0.01 mg/dL Standard Deviation 9.46

SECONDARY outcome

Timeframe: 2 weeks

Population: The 2 week (visit 2) laboratory draw was unable to be obtained for 1 participant, yielding n=12 analyzed for this outcome

change in fasting plasma insulin concentration following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])

Outcome measures

Outcome measures
Measure	Vitamin E Supplementation n=12 Participants Daily oral supplementation with Vitamin E (alpha-tocopherol) for 2 weeks. 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.
Fasting Plasma Insulin Concentration	-2.4 uIU/mL Standard Error 4.4

SECONDARY outcome

Timeframe: 2 weeks

Population: Per the study protocol, the oral protein tolerance test was not repeated at 2 weeks (visit 2) if the baseline (visit 1) oral protein tolerance test was not tolerated. Of the 13 participants who completed the study, 7 did not tolerate the baseline (visit 1) oral protein tolerance test. The 2 week (visit 2) oral protein tolerance test was performed in 6 participants. Oral protein tolerance test parameters were analyzed for these 6 participants.

change in peak plasma insulin concentration during oral protein tolerance test following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])

Outcome measures

Outcome measures
Measure	Vitamin E Supplementation n=6 Participants Daily oral supplementation with Vitamin E (alpha-tocopherol) for 2 weeks. 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.
Peak Plasma Insulin Concentration	-6.3 uIU/mL Standard Deviation 18.2

SECONDARY outcome

Timeframe: 2 weeks

Population: Per the study protocol, the oral protein tolerance test was not repeated at 2 weeks (visit 2) if the baseline (visit 1) oral protein tolerance test was not tolerated. Of the 13 participants who completed the study, 7 did not tolerate the baseline (visit 1) oral protein tolerance test. The 2 week (visit 2) oral protein tolerance test was performed in 6 participants. Oral protein tolerance test parameters were analyzed for these 6 participants.

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 \[visit 1\])

Outcome measures

Outcome measures
Measure	Vitamin E Supplementation n=6 Participants Daily oral supplementation with Vitamin E (alpha-tocopherol) for 2 weeks. 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.
Delta-plasma Insulin Concentration	-5.2 uIU/mL Standard Deviation 16.5

SECONDARY outcome

Timeframe: 2 weeks

Population: The 2 week (visit 2) laboratory draw was unable to be obtained for 1 participant, yielding n=12 analyzed for this outcome

change in fasting plasma ammonia concentration following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])

Outcome measures

Outcome measures
Measure	Vitamin E Supplementation n=12 Participants Daily oral supplementation with Vitamin E (alpha-tocopherol) for 2 weeks. 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.
Fasting Plasma Ammonia Concentration	1.0 micromolar Standard Deviation 31.6

SECONDARY outcome

Timeframe: 2 weeks

Population: The 2 week (visit 2) plasma ammonia at 60 minutes was not obtained in 1 participant in whom the visit 2 oral protein tolerance test was performed, yielding n=5 for analysis of this outcome.

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 \[visit 1\])

Outcome measures

Outcome measures
Measure	Vitamin E Supplementation n=5 Participants Daily oral supplementation with Vitamin E (alpha-tocopherol) for 2 weeks. 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.
Delta-plasma Ammonia Concentration	-3.4 micromolar Standard Deviation 15.5

SECONDARY outcome

Timeframe: 2 weeks

Population: Home glucose meter testing was not performed by 3 participants, yielding n=10 analyzed for this outcome.

change in frequency of hypoglycemia (plasma glucose \<70 mg/dL) detected on home glucose meter following Vitamin E supplementation (2 weeks \[visit 2\] - baseline \[visit 1\])