NCT06130228 - Nutritional Therapy in Late-onset Pompe Disease | Crick | Crick

Nutritional Therapy in Late-onset Pompe Disease

Phase 2UnknownNCT06130228

McMaster University28 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

Outcomes

Primary Outcomes

Percent change in the body composition index by DEXA analyses

Body composition index (lean mass/fat mass ratio)

Time frame: Baseline to 4 months

Percent change in seated pulmonary function by spirometry

Seated forced expiratory volume/forced vital capacity ratio (FEV1/FVC)

Time frame: Baseline to 4 months

Percent change in supine pulmonary function by spirometry

Supine forced expiratory volume/forced vital capacity ratio (FEV1/FVC)

Time frame: Baseline to 4 months

Percent change in 6-minute walking test distance

6-minute walking test distance (meters)

Time frame: Baseline to 4 months

Secondary Outcomes

Percent change in health-related quality of life by SF-36 Survey

36-item short form survey (ranging from low 0 to high 100)

Time frame: Baseline to 4 months

Percent change in health-related quality of life by Rotterdam Handicap Score

Rotterdam Handicap Score (ranging from low 9 to high 36)

Time frame: Baseline to 4 months

Percent change in health-related quality of life by the R-Pact Questionnaire

Rasch-built Pompe-specific Activity (ranging from low 0 to high 100 points)

Time frame: Baseline to 4 months

Percent change in maximal grip strength by dynamometry

Maximal grip strength (kilogram)

Time frame: Baseline to 4 months

Percent change in isometric leg strength by Biodex

Isometric leg strength (newton meters)

Time frame: Baseline to 4 months

Percent change in leg strength by 4-step stair climb test

4-step stair climb time (seconds)

Time frame: Baseline to 4 months

Percent change in lower extremity functioning by short physical performance battery (SPPB)

Short physical performance battery (ranging from low 0 to high 12)

Time frame: Baseline to 4 months

Percent change in lower extremity functioning by timed get up and go test (TUG)

Timed get up and go test (seconds)

Time frame: Baseline to 4 months

Percent change in total muscle glycogen by ELISA

Total muscle glycogen (ug per mg of tissue)

Time frame: Baseline to 4 months

Percent change in lysosomal glycogen in muscle by high-resolution light microscopy

Lysosomal glycogen (% total muscle area)

Time frame: Baseline to 4 months

Percent change in autophagic area in muscle by electron microscopy

Autopgahic area (% total muscle area)

Time frame: Baseline to 4 months

Percent change in p62 expression in muscle by Western blotting

p62 expression (optical density)

Time frame: Baseline to 4 months

Percent change in complex I-V expression in muscle by Western blotting

Complex I-V expression (optical density)

Time frame: Baseline to 4 months

Percent change in 4-hydroxynonenal levels in muscle by Western blotting

4-hydroxynonenal levels (optical density)

Time frame: Baseline to 4 months

Percent change in galactin-3 expression in muscle by Western blotting

Galactin-3 expression (optical density)

Time frame: Baseline to 4 months

Percent change in superoxide dismutase 1 expression in muscle by Western blotting

Superoxide dismutase 1 expression (optical density)

Time frame: Baseline to 4 months

Percent change in superoxide dismutase 2 expression in muscle by Western blotting

Superoxide dismutase 2 expression (optical density)

Time frame: Baseline to 4 months