Vitamin E Supplementation in Hyperinsulinism/Hyperammonemia Syndrome

NCT03797222 | Completed Results

• 2 other identifiers: 17-014550T32DK063688
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

Investigators will assess the tolerability of oral Vitamin E supplementation in subjects with congenital hyperinsulinism (HI) and hyperammonemia (HA) syndrome.

Conditions

Hyperinsulinism-Hyperammonemia Syndrome

Keywords

hyperinsulinism; hyperammonemia; hypoglycemia; vitamin e

Outcome Measures

Primary Outcomes (1)

• 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.

  2 weeks

Secondary Outcomes (10)

• Plasma Alpha-tocopherol Concentration

  2 weeks

• Delta-plasma Glucose Concentration

  2 weeks

• Fasting Plasma Glucose Concentration

  2 weeks

• Nadir Plasma Glucose Concentration

  2 weeks

• Fasting Plasma Insulin Concentration

  2 weeks

Study Arms (1)

Vitamin E Supplementation

EXPERIMENTAL

Daily oral supplementation with Vitamin E (alpha-tocopherol) for 2 weeks.

Dietary Supplement: Vitamin E

Interventions

Vitamin E DIETARY_SUPPLEMENT

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

Vitamin E Supplementation

Eligibility Criteria

• Age: 1 Year - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Individuals age ≥12 months and ≤40 years
• Diagnosis of HI/HA syndrome
• On diazoxide therapy for treatment of hypoglycemia
• Females ≥11 years of age or menstruating must have a negative urine/serum 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.
• Informed consent for participants ≥18 years. Parental/guardian permission (informed consent) and, if appropriate, child assent for participants \<18 years.

You may not qualify if:

• Individuals age \<12 months or \>40 years
• Individuals who have experienced an allergic reaction to Vitamin E
• Individuals with a known allergy to dairy, whey, or soy
• On concurrent therapy with a medication known to be metabolized by the CYP3A pathway
• Individuals with a known increased risk of bleeding (bleeding disorder or on antiplatelet or anticoagulation therapy)
• Vitamin E supplementation within 30 days prior to enrollment, including multivitamins containing Vitamin E
• Severe hypoglycemia (plasma glucose \<50 mg/dL on repeat checks using home glucose meter) more than once weekly within 30 days prior to enrollment.
• 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.
• Evidence of severe hematologic abnormality including severe anemia and/or thrombocytopenia.
• Any investigational drug use within 30 days prior to enrollment.
• Pregnant or lactating females.
• Parents/guardians or 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).
• Parents/guardians or subjects with limited English proficiency.

Sponsors & Collaborators

• Elizabeth A Rosenfeld: lead
• University of Pennsylvania: collaborator
• Lawson Wilkins Pediatric Endocrine Society: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

Related Publications (10)

• 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.

  PMID: 20936362 BACKGROUND

• Snider 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.

  PMID: 23275527 BACKGROUND

• Hsu 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.

  PMID: 11241047 BACKGROUND

• Stanley CA, Baker L. Hyperinsulinism in infancy: diagnosis by demonstration of abnormal response to fasting hypoglycemia. Pediatrics. 1976 May;57(5):702-11.

  PMID: 940710 BACKGROUND

• Li 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.

  PMID: 19531491 BACKGROUND

• McBurney MI, Yu EA, Ciappio ED, Bird JK, Eggersdorfer M, Mehta S. Suboptimal Serum alpha-Tocopherol Concentrations Observed among Younger Adults and Those Depending Exclusively upon Food Sources, NHANES 2003-20061-3. PLoS One. 2015 Aug 19;10(8):e0135510. doi: 10.1371/journal.pone.0135510. eCollection 2015.

  PMID: 26287975 BACKGROUND

• Ulatowski L, Manor D. Vitamin E trafficking in neurologic health and disease. Annu Rev Nutr. 2013;33:87-103. doi: 10.1146/annurev-nutr-071812-161252. Epub 2013 Apr 29.

  PMID: 23642196 BACKGROUND

• Pfeiffer CM, Sternberg MR, Schleicher RL, Haynes BM, Rybak ME, Pirkle JL. The CDC's Second National Report on Biochemical Indicators of Diet and Nutrition in the U.S. Population is a valuable tool for researchers and policy makers. J Nutr. 2013 Jun;143(6):938S-47S. doi: 10.3945/jn.112.172858. Epub 2013 Apr 17.

  PMID: 23596164 BACKGROUND

• Ferslew 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.

  PMID: 8429120 BACKGROUND

• Treberg 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.

  PMID: 20332361 BACKGROUND

MeSH Terms

Conditions

Hyperinsulinemic hypoglycemia, familial, 6; Hyperinsulinism; Hyperammonemia; Hypoglycemia

Interventions

Vitamin E; alpha-Tocopherol

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tocopherols

Results Point of Contact

• Title: Lauren Mitteer
• Organization: Children's Hospital of Philadelphia

mitteerl@chop.edu

215-590-3174

Study Officials

• Elizabeth Rosenfeld, MD

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Attending Physician

Model Details: This open-label tolerability and feasibility pilot clinical study will use a before-and-after design, with blood tests and fasting oral protein tolerance test performed prior to and after 2 weeks of daily oral Vitamin E supplementation in individuals with HI/HA syndrome.

Study Record Dates

• First Submitted: January 6, 2019
• First Posted: January 9, 2019
• Study Start: April 15, 2019
• Primary Completion: March 23, 2020
• Study Completion: March 23, 2020
• Last Updated: November 25, 2022
• Results First Posted: November 25, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)