Multi-ingredient Supplementation as an Adjunctive Therapy in Late-onset Pompe Disease
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 28
- 主要终点
- Percent change in seated pulmonary function by spirometry
研究概览
简要总结
RATIONALE: Pompe disease (PD) is a recessive genetic disorder wherein the body cannot break down glycogen due to a mutation in the acid alpha glucosidase (GAA) gene, which encodes for acid alpha-glucosidase. The adult/late onset form (LOPD) leads to glycogen accumulation and autophagic buildup, causing progressive muscle weakness that leads to wheelchair dependence, reduced quality of life and premature death due to cardiorespiratory insufficiency. While nutritional strategies, such as the low carbohydrate/high protein and ketogenic diets, have been used clinically, they are difficult to maintain and have limited benefits. Multi-ingredient supplementation (MIS) allows for targeting of several underlying pathogenic pathways and may be more convenient than traditional dietary strategies, thereby improving both adherence and LOPD pathology.
详细描述
DESIGN AND INTERVENTION: The present study is a 4-month randomized, double-blind, placebo-controlled clinical trial (RCT) with sampling pre and post intervention in late onset Pompe disease patients undergoing enzyme replacement therapy (ERT) (21-90 years of age). Each patient will be randomized into either a Pompe-Targeted Multi-Ingredient Supplement (PDT-MIS; high-quality proteins, antioxidants, plant extracts, vitamins, and omega-3 fatty acids,) or placebo (PLA; collagen, safflower, and cellulose) group and then undergo four months of daily supplementation with concurrent rehabilitative exercise training (mixed cardio and strength four days/week) and respiratory muscle training (four days/week).
GENERAL RESEARCH AIMS AND HYPOTHESIS: The purpose of this study is to investigate the benefits of PDT-MIS on muscle and blood pathology, muscle function, respiratory capacity, and health-related quality of life (HRQOL) in LOPD patients on enzyme replacement therapy (ERT). It is generally hypothesized that PTD-MIS will mitigate mitochondrial dysfunction, oxidative damage, inflammation and alleviate 'autophagic block' in skeletal muscle of LOPD patients. PDT-MIS may therefore improve muscle pathology by affecting several cell pathways simultaneously, and thereby enhance muscle function, respiratory capacity, and HRQOL of LOPD patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Following medical screening and consent, all patients accepted into the study will be assigned a unique identifier number (1-28), which will be provided to an outside party not associated with Dr. Tarnopolsky or co-investigators that will randomize each subject to one of two experimental conditions. Dr. Tarnopolsky, co-investigators, and the subjects will be blinded to the treatment allocations for the duration of the 4-month trial.
入排标准
- 年龄范围
- 21 Years 至 90 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Genetically confirmed LOPD
- •Have undergone enzyme replacement therapy for at least three months.
- •Physically capable of doing rehabilitative exercise, respiratory muscle training, and the clinical tests described herein.
排除标准
- •Dairy protein allergy
- •Renal disease (creatinine > 140)
- •Attempting pregnancy or currently pregnant
- •Current supplementation
结局指标
主要结局
Percent change in seated pulmonary function by spirometry
时间窗: Baseline to 4 months
Seated forced expiratory volume/forced vital capacity ratio (FEV1/FVC)
Percent change in the body composition index by DEXA analyses
时间窗: Baseline to 4 months
Body composition index (lean mass/fat mass ratio)
Percent change in supine pulmonary function by spirometry
时间窗: Baseline to 4 months
Supine forced expiratory volume/forced vital capacity ratio (FEV1/FVC)
Percent change in 6-minute walking test distance
时间窗: Baseline to 4 months
6-minute walking test distance (meters)
次要结局
- Percent change in leg strength by 4-step stair climb test(Baseline to 4 months)
- Percent change in lysosomal glycogen in muscle by high-resolution light microscopy(Baseline to 4 months)
- Percent change in health-related quality of life by the R-Pact Questionnaire(Baseline to 4 months)
- Percent change in maximal grip strength by dynamometry(Baseline to 4 months)
- Percent change in health-related quality of life by Rotterdam Handicap Score(Baseline to 4 months)
- Percent change in isometric leg strength by Biodex(Baseline to 4 months)
- Percent change in lower extremity functioning by timed get up and go test (TUG)(Baseline to 4 months)
- Percent change in autophagic area in muscle by electron microscopy(Baseline to 4 months)
- Percent change in galactin-3 expression in muscle by Western blotting(Baseline to 4 months)
- Percent change in p62 expression in muscle by Western blotting(Baseline to 4 months)
- Percent change in health-related quality of life by SF-36 Survey(Baseline to 4 months)
- Percent change in lower extremity functioning by short physical performance battery (SPPB)(Baseline to 4 months)
- Percent change in total muscle glycogen by ELISA(Baseline to 4 months)
- Percent change in complex I-V expression in muscle by Western blotting(Baseline to 4 months)
- Percent change in 4-hydroxynonenal levels in muscle by Western blotting(Baseline to 4 months)
- Percent change in superoxide dismutase 1 expression in muscle by Western blotting(Baseline to 4 months)
- Percent change in superoxide dismutase 2 expression in muscle by Western blotting(Baseline to 4 months)
研究者
Mark Tarnopolsky
Professor
McMaster University