Nutritional Therapy in Late-onset Pompe Disease

Obesity Clinical Trial

— PDT-MIS  

Official title:

Multi-ingredient Supplementation as an Adjunctive Therapy in Late-onset Pompe Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06130228
• Other study ID #: 17004
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: April 1, 2024
• Est. completion date: April 1, 2025

Study information

• Verified date: November 2023
• Source: McMaster University
• Contact: Mark A Tarnopolsky, MD/PhD
• Phone: 9055212100
• Email: tarnopol[@]mcmaster.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 28
• Est. completion date: April 1, 2025
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Disease
• Glycogen Storage Disease
• Glycogen Storage Disease Type II
• Glycogen Storage Disease Type II, Adult
• Lysosomal Storage Diseases
• Malnutrition
• Metabolic Diseases
• Muscle Loss
• Nutrition Poor
• Obesity
• Pompe Disease

Intervention

Dietary Supplement:
• Multi-ingredient supplement (PDT-MIS)
Supplementation with active PDT-MIS daily
• Placebo (PLA)
Supplementation with inactive placebo

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
McMaster University

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Percent change in malondialdehyde levels in blood	Malondialdehyde levels (ng/mL)	Baseline to 4 months
Other	Percent change in Oxygen Radical Absorbance Capacity in blood	Oxygen Radical Absorbance Capacity (relative fluorescence units)	Baseline to 4 months
Other	Percent change in interleukin 6 levels in blood	interleukin 6 levels (pg/dL)	Baseline to 4 months
Other	Percent change in interleukin 1 levels in blood	interleukin 1 levels (pg/dL)	Baseline to 4 months
Other	Percent change in interleukin 10 levels in blood	interleukin 10 levels (pg/dL)	Baseline to 4 months
Other	Percent change in tumor necrosis factor alpha levels in blood	tumor necrosis factor alpha (pg/dL)	Baseline to 4 months
Other	Percent change in c-reactive protein levels in blood	c-reactive protein levels (mg/dL)	Baseline to 4 months
Primary	Percent change in the body composition index by DEXA analyses	Body composition index (lean mass/fat mass ratio)	Baseline to 4 months
Primary	Percent change in seated pulmonary function by spirometry	Seated forced expiratory volume/forced vital capacity ratio (FEV1/FVC)	Baseline to 4 months
Primary	Percent change in supine pulmonary function by spirometry	Supine forced expiratory volume/forced vital capacity ratio (FEV1/FVC)	Baseline to 4 months
Primary	Percent change in 6-minute walking test distance	6-minute walking test distance (meters)	Baseline to 4 months
Secondary	Percent change in health-related quality of life by SF-36 Survey	36-item short form survey (ranging from low 0 to high 100)	Baseline to 4 months
Secondary	Percent change in health-related quality of life by Rotterdam Handicap Score	Rotterdam Handicap Score (ranging from low 9 to high 36)	Baseline to 4 months
Secondary	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)	Baseline to 4 months
Secondary	Percent change in maximal grip strength by dynamometry	Maximal grip strength (kilogram)	Baseline to 4 months
Secondary	Percent change in isometric leg strength by Biodex	Isometric leg strength (newton meters)	Baseline to 4 months
Secondary	Percent change in leg strength by 4-step stair climb test	4-step stair climb time (seconds)	Baseline to 4 months
Secondary	Percent change in lower extremity functioning by short physical performance battery (SPPB)	Short physical performance battery (ranging from low 0 to high 12)	Baseline to 4 months
Secondary	Percent change in lower extremity functioning by timed get up and go test (TUG)	Timed get up and go test (seconds)	Baseline to 4 months
Secondary	Percent change in total muscle glycogen by ELISA	Total muscle glycogen (ug per mg of tissue)	Baseline to 4 months
Secondary	Percent change in lysosomal glycogen in muscle by high-resolution light microscopy	Lysosomal glycogen (% total muscle area)	Baseline to 4 months
Secondary	Percent change in autophagic area in muscle by electron microscopy	Autopgahic area (% total muscle area)	Baseline to 4 months
Secondary	Percent change in p62 expression in muscle by Western blotting	p62 expression (optical density)	Baseline to 4 months
Secondary	Percent change in complex I-V expression in muscle by Western blotting	Complex I-V expression (optical density)	Baseline to 4 months
Secondary	Percent change in 4-hydroxynonenal levels in muscle by Western blotting	4-hydroxynonenal levels (optical density)	Baseline to 4 months
Secondary	Percent change in galactin-3 expression in muscle by Western blotting	Galactin-3 expression (optical density)	Baseline to 4 months
Secondary	Percent change in superoxide dismutase 1 expression in muscle by Western blotting	Superoxide dismutase 1 expression (optical density)	Baseline to 4 months
Secondary	Percent change in superoxide dismutase 2 expression in muscle by Western blotting	Superoxide dismutase 2 expression (optical density)	Baseline to 4 months