Browsing by Author "Batten, Milisa T"

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    Respiratory muscle training (RMT) in late-onset Pompe disease (LOPD): A protocol for a sham-controlled clinical trial.
    (Molecular genetics and metabolism, 2019-08) Jones, Harrison N; Kuchibhatla, Maragatha; Crisp, Kelly D; Hobson Webb, Lisa D; Case, Laura; Batten, Milisa T; Marcus, Jill A; Kravitz, Richard M; Kishnani, Priya S

    Introduction

    Morbidity and mortality in adults with late-onset Pompe disease (LOPD) results primarily from persistent progressive respiratory muscle weakness despite treatment with enzyme replacement therapy (ERT). To address this need, we have developed a 12-week respiratory muscle training (RMT) program that provides calibrated, individualized, and progressive pressure-threshold resistance against inspiration and expiration. Our previous results suggest that our RMT regimen is safe, well-tolerated, and results in large increases in respiratory muscle strength. We now conduct an exploratory double-blind, randomized control trial (RCT) to determine: 1) utility and feasibility of sham-RMT as a control condition, 2) the clinically meaningful outcome measures for inclusion in a future efficacy trial. This manuscript provides comprehensive information regarding the design and methods used in our trial and will aid in the reporting and interpretation of our future findings.

    Methods

    Twenty-eight adults with LOPD will be randomized (1:1) in blocks of 4 to RMT (treatment) or sham-RMT (control). Assessments will be conducted at pretest, posttest, 3-months detraining, and 6-months detraining. The primary outcome is maximum inspiratory pressure (MIP). Secondary outcomes include maximum expiratory pressure (MEP), 6-min walk test (6MWT), Gait, Stairs, Gowers, and Chair test (GSGC), peak cough flow (PCF), and patient-reported life activity/social participation (Rasch-built Pompe-specific Activity scale [R-Pact]). Exploratory outcomes include quantitative measures from polysomnography; patient reported measures of fatigue, daytime sleepiness, and sleep quality; and ultrasound measures of diaphragm thickness. This research will use a novel tool to provide automated data collection and user feedback, and improve control over dose.

    Ethics and dissemination

    The results of this clinical trial will be promptly analyzed and submitted for publication. Results will also be made available on clinicaltrials.gov. ClinicalTrials.gov: NCT02801539, R21AR069880.
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    Respiratory muscle training in late-onset Pompe disease: Results of a sham-controlled clinical trial.
    (Neuromuscular disorders : NMD, 2020-11) Jones, Harrison N; Kuchibhatla, Maragatha; Crisp, Kelly D; Hobson-Webb, Lisa D; Case, Laura; Batten, Milisa T; Marcus, Jill A; Kravitz, Richard M; Kishnani, Priya S
    To address progressive respiratory muscle weakness in late-onset Pompe disease (LOPD), we developed a 12-week respiratory muscle training (RMT) program. In this exploratory, double-blind, randomized control trial, 22 adults with LOPD were randomized to RMT or sham-RMT. The primary outcome was maximum inspiratory pressure (MIP). Secondary and exploratory outcomes included maximum expiratory pressure (MEP), peak cough flow, diaphragm ultrasound, polysomnography, patient-reported outcomes, and measures of gross motor function. MIP increased 7.6 cmH2O (15.9) in the treatment group and 2.7 cmH2O (7.6) in the control group (P = 0.4670). MEP increased 14.0 cmH2O (25.9) in the treatment group and 0.0 cmH2O (12.0) in the control group (P = 0.1854). The only statistically significant differences in secondary/exploratory outcomes were improvements in time to climb 4 steps (P = 0.0346) and daytime sleepiness (P = 0.0160). The magnitude of changes in MIP and MEP in the treatment group were consistent with our pilot findings but did not achieve statistical significance in comparison to controls. Explanations for this include inadequate power and baseline differences in subject characteristics between groups. Additionally, control group subjects appeared to exhibit an active response to sham-RMT and therefore sham-RMT may not be an optimal control condition for RMT in LOPD.
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    Tongue weakness and atrophy differentiates late-onset Pompe disease from other forms of acquired/hereditary myopathy.
    (Molecular genetics and metabolism, 2021-07) Jones, Harrison N; Hobson-Webb, Lisa D; Kuchibhatla, Maragatha; Crisp, Kelly D; Whyte-Rayson, Ashley; Batten, Milisa T; Zwelling, Paul J; Kishnani, Priya S
    Late-onset Pompe disease (LOPD) is an inherited autosomal recessive progressive metabolic myopathy that presents in the first year of life to adulthood. Clinical presentation is heterogeneous, differential diagnosis is challenging, and diagnostic delay is common. One challenge to differential diagnosis is the overlap of clinical features with those encountered in other forms of acquired/hereditary myopathy. Tongue weakness and imaging abnormalities are increasingly recognized in LOPD. In order to explore the diagnostic potential of tongue involvement in LOPD, we assessed tongue structure and function in 70 subjects, including 10 with LOPD naive to treatment, 30 with other acquired/hereditary myopathy, and 30 controls with neuropathy. Tongue strength was assessed with both manual and quantitative muscle testing. Ultrasound (US) was used to assess tongue overall appearance, echointensity, and thickness. Differences in tongue strength, qualitative appearance, echointensity, and thickness between LOPD subjects and neuropathic controls were statistically significant. Greater tongue involvement was observed in LOPD subjects compared to those with other acquired/hereditary myopathies, based on statistically significant decreases in quantitative tongue strength and sonographic muscle thickness. These findings provide additional evidence for tongue involvement in LOPD characterized by weakness and sonographic abnormalities suggestive of fibrofatty replacement and atrophy. Findings of quantitative tongue weakness and/or atrophy may aid differentiation of LOPD from other acquired/hereditary myopathies. Additionally, our experiences in this study reveal US to be an effective, efficient imaging modality to allow quantitative assessment of the lingual musculature at the point of care.