Clinical trial NCT06130228: Nutritional Therapy in Late-onset Pompe Disease
Official title: Multi-ingredient Supplementation as an Adjunctive Therapy in Late-onset Pompe Disease
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Pompe Disease
Muscle Loss
Obesity
Nutrition Poor
Lysosomal Storage Diseases
Glycogen Storage Disease Type II
Glycogen Storage Disease Type II Late Onset
Glycogen Storage Disease Type II, Adult
Keywords: Muscle
Supplements
Antioxidants
Whey
Casein
Vitamin D
Creatine
Calcium
Omega-3
Green coffee bean
Green tea
CoQ10
Alpha-lipoic acid
Vitamin E
Weight loss
Obesity
Muscle strength
6-meter walk test
Pompe disease
Oxidative stress
Mitochondria
Autophagy
Glycogen
Forskolin
Beet root
Performance
Lead sponsor: McMaster University
Sponsor class: OTHER
First posted: 2023-11-14
Enrollment: 28
Sex: ALL
Minimum age (years): 21
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The present study is a 4-month randomized double-blind, placebo controlled, clinical trial with two treatments arms and groups (PDT-MIS and PLA).
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* Dairy protein allergy
* Renal disease (creatinine \> 140)
* Attempting pregnancy or currently pregnant
* Current supplementation

Primary outcomes:
measure: Percent change in the body composition index by DEXA analyses
timeFrame: Baseline to 4 months
measure: Percent change in seated pulmonary function by spirometry
timeFrame: Baseline to 4 months
measure: Percent change in supine pulmonary function by spirometry
timeFrame: Baseline to 4 months
measure: Percent change in 6-minute walking test distance
timeFrame: Baseline to 4 months
Secondary outcomes:
measure: Percent change in health-related quality of life by SF-36 Survey
timeFrame: Baseline to 4 months
measure: Percent change in health-related quality of life by Rotterdam Handicap Score
timeFrame: Baseline to 4 months
measure: Percent change in health-related quality of life by the R-Pact Questionnaire
timeFrame: Baseline to 4 months
measure: Percent change in maximal grip strength by dynamometry
timeFrame: Baseline to 4 months
measure: Percent change in isometric leg strength by Biodex
timeFrame: Baseline to 4 months
measure: Percent change in leg strength by 4-step stair climb test
timeFrame: Baseline to 4 months
measure: Percent change in lower extremity functioning by short physical performance battery (SPPB)
timeFrame: Baseline to 4 months
measure: Percent change in lower extremity functioning by timed get up and go test (TUG)
timeFrame: Baseline to 4 months
measure: Percent change in total muscle glycogen by ELISA
timeFrame: Baseline to 4 months
measure: Percent change in lysosomal glycogen in muscle by high-resolution light microscopy
timeFrame: Baseline to 4 months
measure: Percent change in autophagic area in muscle by electron microscopy
timeFrame: Baseline to 4 months
measure: Percent change in p62 expression in muscle by Western blotting
timeFrame: Baseline to 4 months
measure: Percent change in complex I-V expression in muscle by Western blotting
timeFrame: Baseline to 4 months
measure: Percent change in 4-hydroxynonenal levels in muscle by Western blotting
timeFrame: Baseline to 4 months
measure: Percent change in galactin-3 expression in muscle by Western blotting
timeFrame: Baseline to 4 months
measure: Percent change in superoxide dismutase 1 expression in muscle by Western blotting
timeFrame: Baseline to 4 months
measure: Percent change in superoxide dismutase 2 expression in muscle by Western blotting
timeFrame: Baseline to 4 months
Other outcomes:
measure: Percent change in malondialdehyde levels in blood
timeFrame: Baseline to 4 months
measure: Percent change in Oxygen Radical Absorbance Capacity in blood
timeFrame: Baseline to 4 months
measure: Percent change in interleukin 6 levels in blood
timeFrame: Baseline to 4 months
measure: Percent change in interleukin 1 levels in blood
timeFrame: Baseline to 4 months
measure: Percent change in interleukin 10 levels in blood
timeFrame: Baseline to 4 months
measure: Percent change in tumor necrosis factor alpha levels in blood
timeFrame: Baseline to 4 months
measure: Percent change in c-reactive protein levels in blood
timeFrame: Baseline to 4 months
Locations:
Study officials:
affiliation: McMaster University
name: Mark Tarnopololsky, MD/PhD
role: PRINCIPAL_INVESTIGATOR
References: