An Open Label, Exploratory, Proof-of Concept Study of Triheptanoin as Treatment for Patients With Primary-Specific Pyruvate Dehydrogenase Complex (PDC) Deficiency
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Normalization of biochemical markers of disease (β-hydroxybutyrate level)
研究概览
简要总结
This is a medical research study to test a medication in patients with a disease called Pyruvate Dehydrogenase Complex (PDC) Deficiency. The medication is triheptanoin, which is currently FDA approved for the treatment of Long-Chain Fatty Acid Oxidation Disorders. Previous research suggests that triheptanoin may also be effective in the treatment PDC Deficiency. This study will investigate the safety and efficacy (how well it works) of triheptanoin in patients with PDC Deficiency.
详细描述
Participation in the study will require the patient to participate in up to 10 visits over a two-year period. Five of those visits must be done at the UPMC Children's Hospital of Pittsburgh (CHP). Other visits can take place at CHP or remotely. All of these visits will include blood draws.
Triheptanoin will be added to the patients' diet and administered at least 4 times per day. The target dose will be 1.2-3.9 g of triheptanoin per kg body weight with a max goal dose of about 4 g/kg per day.
The triheptanoin will be provided to the patients at no cost. All other costs will be billed to the patients' insurance.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 1 Year 至 17 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 1 year to <18 years of age
- •Subjects with PDCD would need to have a metabolic physician following their clinical care needs prior to their enrollment in the study
- •Diagnosis of PDCD by molecular genetic confirmation of PDHA1, PDHB, DLAT, PDHX, or PDP1 mutation
- •Not pregnant or lactating
- •Parental permission and assent of minor and willingness to comply with study procedures
- •Not participating in any interventional treatment clinical trials
- •Not a recipient of gene therapy, organ transplant, or bone-marrow transplantation
- •If currently on any investigational drugs or therapies, must complete a 30-day washout period prior to Intake & Dosing (Day 1).
- •Negative pregnancy test for all female patients of childbearing age. Individuals of childbearing potential must agree to use a highly effective method of contraception, and males must agree not to father a child or donate sperm. True abstinence for the duration of the study will also be accepted.
- •Subjects are following some form or type of ketogenic diet at the time of the screening visit.
排除标准
- •Diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD)
- •Use of alcohol or drugs of abuse
- •Evidence of liver disease as defined by elevations of AST or ALT >2x ULN in the past 6 months
- •Pregnant, breastfeeding, or lactating females
- •On any investigational product research study (and not completed the required 30-day washout period prior to Intake & Dosing) or recipient of gene therapy or organ or bone-marrow transplantation
研究组 & 干预措施
Triheptanoin
Open label study
干预措施: Triheptanoin (Drug)
结局指标
主要结局
Normalization of biochemical markers of disease (β-hydroxybutyrate level)
时间窗: 24 months
Change in β-hydroxybutyrate levels, comparing results from before and after triheptanoin is initiated - this will be measured by the number of participants who experience any change; measured in mmol/L
Number of participants who report side-effects related to gastrointestinal (GI) distress
时间窗: 24 months
Normalization of biochemical markers of disease (Alanine/Proline ratio)
时间窗: 24 months
Change in Alanine/Proline ratios, comparing results from before and after triheptanoin is initiated - this will be measured by the number of participants who experience any change; measured in μmol/L
Normalization of biochemical markers of disease (lactate)
时间窗: 24 months
Change in lactate levels, comparing results from before and after triheptanoin is initiated - this will be measured by the number of participants who experience any change; measured in mmol/L
Normalization of biochemical markers of disease (Alanine/Lysine ratio)
时间窗: 24 months
Change in Alanine/Lysine ratios, comparing results from before and after triheptanoin is initiated - this will be measured by the number of participants who experience any change; measured in μmol/L
Normalization of biochemical markers of disease (pyruvate)
时间窗: 24 months
Change in pyruvate levels, comparing results from before and after triheptanoin is initiated - this will be measured by the number of participants who experience any change; measured in mg/dl
Normalization of biochemical markers of disease (Alanine/Leucine ratio)
时间窗: 24 months
Change in Alanine/Leucine ratios, comparing results from before and after triheptanoin is initiated - this will be measured by the number of participants who experience any change; measured in μmol/L
More efficacious seizure control
时间窗: 24 months
Measured by a reduction or alteration of home antiepileptics use, from before and after triheptanoin is initiated
More efficacious metabolic control
时间窗: 24 months
Measured by a reduction in episodes of metabolic decompensation, from before and after triheptanoin is initiated
More efficacious disease control
时间窗: 24 months
Measured by a reduction in the frequency of disease related hospitalizations, from before and after triheptanoin is initiated
次要结局
- Improved long-term maintenance and tolerance of diet(24 months)
- Improved quality of life(24 months)
研究者
Jirair Krikor Bedoyan
Associate Professor of Pediatrics
University of Pittsburgh