A Pilot Study of Pyridostigmine in Pompe Disease
Information source: University of Florida
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Pompe Disease
Intervention: Pyridostigmine Bromide (Drug)
Phase: Phase 0
Status: Not yet recruiting
Sponsored by: University of Florida Official(s) and/or principal investigator(s): Barry J Byrne, MD, PhD, Principal Investigator, Affiliation: University of Florida
Overall contact: Katie Faris, BA, Phone: 352-273-7573, Email: kfaris10@ufl.edu
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.
Clinical Details
Official title: Evaluation of Respiratory and Skeletal Muscle Functions in Response to Acetylcholinesterase Inhibitors in Pompe Disease
Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Change in skeletal muscle function (6 Minute Walk Test)(QMT)Change in respiratory function (maximal inspiratory pressure, maximal expiratory pressure, and vital capacity) Change in quality of life [short form 36 (SF-36)] Evaluate the acute effects of pyridostigmine on neuromuscular junction transmission (Single-fiber EMG)
Detailed description:
Pompe is a rare disease, which occurs in approximately 1 per 40,000 births. It is a
progressive and often fatal neuromuscular disorder resulting from mutation in the gene for
acid alpha-glucosidase (GAA), an enzyme necessary to degrade glycogen. Accumulation of
glycogen in multiple tissues results in cardiac, respiratory and skeletal muscle
dysfunction. Enzyme replacement therapy (ERT) is currently the only treatment available, and
although it prolongs survival, adjuvant therapies are needed to help alleviate the dire
symptoms of Pompe disease.
Recent data has revealed that degradation of the neuromuscular junction (NMJ) occurs in
Pompe disease. Acetylcholinesterase inhibitors (AChEI) are substances that inhibit the AChE
enzyme from degrading acetylcholine at the NMJ, and thus increase the functional impact of
this neurotransmitter. AChEI are established as a beneficial therapy for individuals with
primary diseases of the NMJ, such as myasthenia gravis. Recently, administration of an AChEI
was demonstrated to improve NMJ pathology in both mice and individuals affected by other
congenital myopathies, including autosomal centronuclear myopathies (CNM), X-linked
myotubular myopathy (XLMTM) and mutation of tropomyosin 3 (TPM3). Specifically, both NMJ
transmission and motor function were improved. These studies demonstrate that AChEI can be
beneficial in myopathy associated with NMJ pathology.
In this study, we will study the acute effects of pyridostigmine on neuromuscular
transmission, as well as the prolonged effects on respiratory function, skeletal muscle
function and quality of life over a 90 day treatment period.
This project focuses on developing an adjuvant treatment to ERT that targets dysfunction at
the NMJ. Our ultimate goal is to reduce the deleterious consequences of Pompe disease and
improve the overall quality and duration of life in affected individuals.
Eligibility
Minimum age: 8 Years.
Maximum age: 60 Years.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Males or females between 8 and 60 years of age;
2. Diagnosis of Pompe disease (protein assay, genotyping, and positive clinical signs)
3. No contraindication to pyridostigmine
Exclusion Criteria:
1. Already receive pyridostigmine as part of their normal clinical care at screening
2. Are pregnant - participants will receive a urine pregnancy test at screening
3. Have received acute administration of antibiotic, corticosteroid, or neuromuscular
blockade medications within 30 days prior to screening
4. Any other concurrent medical condition which, in the opinion of the study team, would
make the subject inappropriate to participate in the assessments
Locations and Contacts
Katie Faris, BA, Phone: 352-273-7573, Email: kfaris10@ufl.edu
University of Florida Clinical Research Center, Gainesville, Florida 32610, United States; Not yet recruiting Katie Faris, BA, Phone: 352-273-7573, Email: kfaris10@ufl.edu Manuela Corti, PT, PhD, Phone: 352-294-5779, Email: m.corti@peds.ufl.edu
Additional Information
Related publications: 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. Review. 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. 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. 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. 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. Review.
Starting date: June 2015
Last updated: February 2, 2015
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