Vitamin E Supplementation in Hyperinsulinism/Hyperammonemia Syndrome
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 14
- 试验地点
- 2
- 主要终点
- Tolerability of Vitamin E Based on Responses to a Subject/Parent-reported Symptom Questionnaire After Vitamin E Supplementation Compared to Baseline
研究概览
简要总结
Investigators will assess the tolerability of oral Vitamin E supplementation in subjects with congenital hyperinsulinism (HI) and hyperammonemia (HA) syndrome.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Other
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 40 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Tolerability of Vitamin E Based on Responses to a Subject/Parent-reported Symptom Questionnaire After Vitamin E Supplementation Compared to Baseline
时间窗: 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.
次要结局
- Peak Plasma Insulin Concentration(2 weeks)
- Plasma Alpha-tocopherol Concentration(2 weeks)
- Fasting Plasma Glucose Concentration(2 weeks)
- Fasting Plasma Insulin Concentration(2 weeks)
- Delta-plasma Glucose Concentration(2 weeks)
- Nadir Plasma Glucose Concentration(2 weeks)
- Delta-plasma Insulin Concentration(2 weeks)
- Hypoglycemia Frequency(2 weeks)
- Fasting Plasma Ammonia Concentration(2 weeks)
- Delta-plasma Ammonia Concentration(2 weeks)
研究者
Elizabeth A Rosenfeld
Attending Physician
Children's Hospital of Philadelphia