PDT-MIS: Nutritional Therapy in Late-onset Pompe Disease

Sponsor

McMaster University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT06130228

Collaborator

(none)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
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	Dietary Supplement: Multi-ingredient supplement (PDT-MIS) Dietary Supplement: Placebo (PLA)	Phase 2

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

28 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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

Masking:

Triple (Participant, Care Provider, Investigator)

Masking Description:

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.

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

Apr 1, 2024

Anticipated Primary Completion Date :

Sep 1, 2024

Anticipated Study Completion Date :

Apr 1, 2025

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Multi-ingredient supplement (PDT-MIS) 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) Supplementation with active PDT-MIS daily
Placebo Comparator: Placebo (PLA) 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) Supplementation with inactive placebo

Arm

Intervention/Treatment

Experimental: Multi-ingredient supplement (PDT-MIS)

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)

Supplementation with active PDT-MIS daily

Placebo Comparator: Placebo (PLA)

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)

Supplementation with inactive placebo

Outcome Measures

Primary Outcome Measures

Percent change in the body composition index by DEXA analyses [Baseline to 4 months]
Body composition index (lean mass/fat mass ratio)
Percent change in seated pulmonary function by spirometry [Baseline to 4 months]
Seated forced expiratory volume/forced vital capacity ratio (FEV1/FVC)
Percent change in supine pulmonary function by spirometry [Baseline to 4 months]
Supine forced expiratory volume/forced vital capacity ratio (FEV1/FVC)
Percent change in 6-minute walking test distance [Baseline to 4 months]
6-minute walking test distance (meters)

Secondary Outcome Measures

Percent change in health-related quality of life by SF-36 Survey [Baseline to 4 months]
36-item short form survey (ranging from low 0 to high 100)
Percent change in health-related quality of life by Rotterdam Handicap Score [Baseline to 4 months]
Rotterdam Handicap Score (ranging from low 9 to high 36)
Percent change in health-related quality of life by the R-Pact Questionnaire [Baseline to 4 months]
Rasch-built Pompe-specific Activity (ranging from low 0 to high 100 points)
Percent change in maximal grip strength by dynamometry [Baseline to 4 months]
Maximal grip strength (kilogram)
Percent change in isometric leg strength by Biodex [Baseline to 4 months]
Isometric leg strength (newton meters)
Percent change in leg strength by 4-step stair climb test [Baseline to 4 months]
4-step stair climb time (seconds)
Percent change in lower extremity functioning by short physical performance battery (SPPB) [Baseline to 4 months]
Short physical performance battery (ranging from low 0 to high 12)
Percent change in lower extremity functioning by timed get up and go test (TUG) [Baseline to 4 months]
Timed get up and go test (seconds)
Percent change in total muscle glycogen by ELISA [Baseline to 4 months]
Total muscle glycogen (ug per mg of tissue)
Percent change in lysosomal glycogen in muscle by high-resolution light microscopy [Baseline to 4 months]
Lysosomal glycogen (% total muscle area)
Percent change in autophagic area in muscle by electron microscopy [Baseline to 4 months]
Autopgahic area (% total muscle area)
Percent change in p62 expression in muscle by Western blotting [Baseline to 4 months]
p62 expression (optical density)
Percent change in complex I-V expression in muscle by Western blotting [Baseline to 4 months]
Complex I-V expression (optical density)
Percent change in 4-hydroxynonenal levels in muscle by Western blotting [Baseline to 4 months]
4-hydroxynonenal levels (optical density)
Percent change in galactin-3 expression in muscle by Western blotting [Baseline to 4 months]
Galactin-3 expression (optical density)
Percent change in superoxide dismutase 1 expression in muscle by Western blotting [Baseline to 4 months]
Superoxide dismutase 1 expression (optical density)
Percent change in superoxide dismutase 2 expression in muscle by Western blotting [Baseline to 4 months]
Superoxide dismutase 2 expression (optical density)

Other Outcome Measures

Percent change in malondialdehyde levels in blood [Baseline to 4 months]
Malondialdehyde levels (ng/mL)
Percent change in Oxygen Radical Absorbance Capacity in blood [Baseline to 4 months]
Oxygen Radical Absorbance Capacity (relative fluorescence units)
Percent change in interleukin 6 levels in blood [Baseline to 4 months]
interleukin 6 levels (pg/dL)
Percent change in interleukin 1 levels in blood [Baseline to 4 months]
interleukin 1 levels (pg/dL)
Percent change in interleukin 10 levels in blood [Baseline to 4 months]
interleukin 10 levels (pg/dL)
Percent change in tumor necrosis factor alpha levels in blood [Baseline to 4 months]
tumor necrosis factor alpha (pg/dL)
Percent change in c-reactive protein levels in blood [Baseline to 4 months]
c-reactive protein levels (mg/dL)

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years to 90 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.