A Pilot Study of Pyridostigmine in Pompe Disease

NCT02357225 | Terminated Early Phase 1

• 1 other identifier: IRB201200154
• Study Type: interventional
• Target: 2
• Locations: 1 country
• Sites: 1

Brief Summary

Pyridostigmine is an acetylcholinesterase inhibitor, which degrades acetylcholine at the neuromuscular junction. Based on recent studies, pyridostigmine may be an effective adjuvant treatment for people with Pompe disease, as it increases the functional impact of this neurotransmitter. Hypothesis: the use of pyridostigmine in Pompe disease will improve transmission of acetylcholine across the neuromuscular junction, skeletal muscle function, respiratory function, and quality of life.

Conditions

Pompe Disease

Keywords

Pompe disease; Pyridostigmine

Outcome Measures

Primary Outcomes (4)

• Change in skeletal muscle function (6 Minute Walk Test)(QMT)

  Quantitative muscle testing and the 6 Minute Walk Test will be used to evaluate skeletal muscle function.

  Baseline, Day 90

• Change in respiratory function (maximal inspiratory pressure, maximal expiratory pressure, and vital capacity)

  Pulmonary function tests, including maximal inspiratory pressure, maximal expiratory pressure, and vital capacity, will be used to evaluate respiratory function

  Baseline, Day 90

• Change in quality of life [short form 36 (SF-36)]

  The short form 36 health survey (SF-36) will be used to evaluate quality of life

  Baseline, Day 90

• Evaluate the acute effects of pyridostigmine on neuromuscular junction transmission (Single-fiber EMG)

  Single-fiber EMG will be performed on the tibialis anterior pre- and 2 hour post-administration of pyridostigmine. MIP and hand grip will also be tested before and after receiving the study drug.

  Baseline

Study Arms (2)

Acute Dose of Pyridostigmine

EXPERIMENTAL

Subjects will receive an acute administration of pyridostigmine bromide, calculated on their body weight at clinical exam (1 mg/kg, 60mg max starting dose), and will be monitored for 2 hours post administration. Subjects will also receive a pre- and post-administration single-fiber EMG, respiratory tests and strength tests in order to evaluate the function of the neuromuscular junction. All study subjects will be enrolled in this arm.

Drug: Pyridostigmine Bromide

Prolonged Use of Pyridostigmine

EXPERIMENTAL

This arm will evaluate the impact of pyridostigmine bromide on respiratory and skeletal muscle function during a 90-day administration period. On Days 1 - 7 subjects will receive 0.5mg/kg of the study drug every 4 hours while awake. On Days 8 - 90 subjects will receive 1.0 mg/kg every 4 hours while awake. Quality of life will also be measured with the SF-36 health survey. Data collection will occur at multiple time points (Days 30 and 90) throughout the study. Subjects will also be contacted at least weekly via telephone. All study subjects will be enrolled in this arm.

Drug: Pyridostigmine Bromide

Interventions

Pyridostigmine Bromide DRUG

Pyridostigmine is an acetylcholinesterase inhibitor, which increases the amount of acetylcholine at the neuromuscular junction. It will be taken orally, either as a tablet or as a syrup.

Also known as: Mestinon

Acute Dose of Pyridostigmine; Prolonged Use of Pyridostigmine

Eligibility Criteria

• Age: 8 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Males or females between 8 and 60 years of age;
• Diagnosis of Pompe disease (protein assay, genotyping, and positive clinical signs)
• No contraindication to pyridostigmine

You may not qualify if:

• Already receive pyridostigmine as part of their normal clinical care at screening
• Are pregnant - participants will receive a urine pregnancy test at screening
• Have received acute administration of antibiotic, corticosteroid, or neuromuscular blockade medications within 30 days prior to screening
• Any other concurrent medical condition which, in the opinion of the study team, would make the subject inappropriate to participate in the assessments

Sponsors & Collaborators

• University of Florida: lead

Study Sites (1)

University of Florida Clinical Research Center

Gainesville, Florida, 32610, United States

Location

Related Publications (5)

• Byrne BJ, Falk DJ, Pacak CA, Nayak S, Herzog RW, Elder ME, Collins SW, Conlon TJ, Clement N, Cleaver BD, Cloutier DA, Porvasnik SL, Islam S, Elmallah MK, Martin A, Smith BK, Fuller DD, Lawson LA, Mah CS. Pompe disease gene therapy. Hum Mol Genet. 2011 Apr 15;20(R1):R61-8. doi: 10.1093/hmg/ddr174. Epub 2011 Apr 25.

  PMID: 21518733 BACKGROUND

• Falk DJ, Todd AG, Lee S, Soustek MS, ElMallah MK, Fuller DD, Notterpek L, Byrne BJ. Peripheral nerve and neuromuscular junction pathology in Pompe disease. Hum Mol Genet. 2015 Feb 1;24(3):625-36. doi: 10.1093/hmg/ddu476. Epub 2014 Sep 12.

  PMID: 25217571 BACKGROUND

• Corti M, Smith BK, Falk DJ, Lawson LA, Fuller DD, Subramony SH, Byrne BJ, Christou EA. Altered activation of the tibialis anterior in individuals with Pompe disease: Implications for motor unit dysfunction. Muscle Nerve. 2015 Jun;51(6):877-83. doi: 10.1002/mus.24444. Epub 2015 Apr 24.

  PMID: 25186912 BACKGROUND

• Robb SA, Sewry CA, Dowling JJ, Feng L, Cullup T, Lillis S, Abbs S, Lees MM, Laporte J, Manzur AY, Knight RK, Mills KR, Pike MG, Kress W, Beeson D, Jungbluth H, Pitt MC, Muntoni F. Impaired neuromuscular transmission and response to acetylcholinesterase inhibitors in centronuclear myopathies. Neuromuscul Disord. 2011 Jun;21(6):379-86. doi: 10.1016/j.nmd.2011.02.012. Epub 2011 Mar 25.

  PMID: 21440438 BACKGROUND

• Maggi L, Mantegazza R. Treatment of myasthenia gravis: focus on pyridostigmine. Clin Drug Investig. 2011 Oct 1;31(10):691-701. doi: 10.2165/11593300-000000000-00000.

  PMID: 21815707 BACKGROUND

MeSH Terms

Conditions

Glycogen Storage Disease Type II

Interventions

Pyridostigmine Bromide

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; Lysosomal Storage Diseases; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Pyridinium Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Barry J Byrne, MD, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 23, 2015
• First Posted: February 6, 2015
• Study Start: August 1, 2015
• Primary Completion: January 1, 2018
• Study Completion: January 1, 2018
• Last Updated: May 15, 2018

Record last verified: 2018-05

Locations

US (1)