Nutritional Therapy in Late-onset Pompe Disease

NCT06130228 | Unknown Phase 2 DMC

• 1 other identifier: 17004
• Study Type: interventional
• Target: 28
• Locations: 0 countries
• Sites: N/A

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.

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

Outcome Measures

Primary Outcomes (4)

• Percent change in the body composition index by DEXA analyses

  Body composition index (lean mass/fat mass ratio)

  Baseline to 4 months

• Percent change in seated pulmonary function by spirometry

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

  Baseline to 4 months

• Percent change in supine pulmonary function by spirometry

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

  Baseline to 4 months

• Percent change in 6-minute walking test distance

  6-minute walking test distance (meters)

  Baseline to 4 months

Secondary Outcomes (17)

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

  Baseline to 4 months

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

  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 isometric leg strength by Biodex

  Baseline to 4 months

Other Outcomes (7)

• Percent change in malondialdehyde levels in blood

  Baseline to 4 months

• Percent change in Oxygen Radical Absorbance Capacity in blood

  Baseline to 4 months

• Percent change in interleukin 6 levels in blood

  Baseline to 4 months

Study Arms (2)

Multi-ingredient supplement (PDT-MIS)

EXPERIMENTAL

Multi-ingredient supplementation (PDT-MIS) consists of daily intake of high-quality proteins, creatine, vitamin D, calcium, plant extracts (green coffee bean, green tea, beet root, and forskolin), and Omega-3 fatty acids. Concurrent with supplementation, patients will do mixed rehabilitative exercise (cardio and strength) and respiratory muscle training four days a week.

Dietary Supplement: Multi-ingredient supplement (PDT-MIS)

Placebo (PLA)

PLACEBO COMPARATOR

Placebo (PLA) consists of daily intake of collagen, safflower, and microcrystalline cellulose. Concurrent with supplementation, patients will do mixed rehabilitative exercise (cardio and strength) and respiratory muscle training four days a week.

Dietary Supplement: Placebo (PLA)

Interventions

Multi-ingredient supplement (PDT-MIS) DIETARY_SUPPLEMENT

Supplementation with active PDT-MIS daily

Multi-ingredient supplement (PDT-MIS)

Placebo (PLA) DIETARY_SUPPLEMENT

Supplementation with inactive placebo

Placebo (PLA)

Eligibility Criteria

• Age: 21 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

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

Sponsors & Collaborators

• McMaster University: lead

MeSH Terms

Conditions

Glycogen Storage Disease Type II; Muscular Atrophy; Obesity; Malnutrition; Lysosomal Storage Diseases; Weight Loss

Condition Hierarchy (Ancestors)

Lysosomal Storage Diseases, Nervous System; Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Glycogen Storage Disease; Carbohydrate Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Neuromuscular Manifestations; Neurologic Manifestations; Atrophy; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Body Weight Changes

Study Officials

• Mark Tarnopololsky, MD/PhD

  McMaster University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mark A Tarnopolsky, MD/PhD

CONTACT

9055212100; tarnopol@mcmaster.ca

Mats I Nilsson, PhD

CONTACT

9055252100; nilsson@mcmaster.ca

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: 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.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: The present study is a 4-month randomized double-blind, placebo controlled, clinical trial with two treatments arms and groups (PDT-MIS and PLA).

Study Record Dates

• First Submitted: November 8, 2023
• First Posted: November 14, 2023
• Study Start: April 1, 2024
• Primary Completion: September 1, 2024
• Study Completion: April 1, 2025
• Last Updated: November 14, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share