Change in MUNIX in Patients With CMT1A Undergoing a Home Ankle Strengthening Program Versus Standard of Care

NCT03715283 | Completed DMC

• 1 other identifier: VR52854
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

Here the investigators aim to show that a focused lower extremity resistance strength training program in patients with Charcot-Marie-Tooth disease (CMT) results in increased motor strength of ankle plantar- and dorsi-flexion. The investigators will use motor unit index MUNIX and hand held dynamometry to correlate strength changes. The investigators believe that increased strength will correlate with an increased motor unit number and as such will prove that axonal renervation or improved recruitment is possible with a focused exercises in patients with CMT. Additionally, the investigators will show that that MUNIX declines over a 12-week period in patients with CMT whom continue standard of care. This will identify MUNIX as a responsive marker for disease progression in addition to detecting functional improvement, which will be valuable for future clinical trials.

Conditions

Charcot-Marie-Tooth Disease

Keywords

MUNIX

Outcome Measures

Primary Outcomes (2)

• Change in motor unit number index (MUNIX) of the peroneal nerve in the treatment arm versus the untreated arm from baseline to 12 weeks (Peroneal Munix at 12 weeks - Peroneal Munix at baseline,0-1,000a.u., higher numbers represent more motor units)

  12 weeks

• Change in motor unit number index (MUNIX) of the tibial nerve in the treatment arm versus the untreated arm from baseline to 12 weeks (Tibial MUNIX.at 12 weeks - Tibial MUNIX at baseline, 0-1000 arbitrary units, higher numbers represent more motor units)

  12 weeks

Secondary Outcomes (18)

• Change in peroneal nerve motor unit number index (MUNIX) at 6 weeks between treatment arms (MUNIX at 6 weeks - MUNIX at Baseline; 0-1000 arbitrary units, higher numbers represent more motor units).

  6 weeks

• Change in tibial nerve compound muscle action potential (CMAP) at 6 weeks between treatment arms ((Tibial CMAP at 6 weeks - Tibial CMAP at baseline (mV) 0-300mV, mV= milliVolts, higher numbers represent more motor units).

  6 weeks

• Change in tibial nerve compound muscle action potential (CMAP) at 12 weeks between treatment arms (Tibial CMAP at 12 weeks - Tibial CMAP at baseline (mV) 0-300mV, mV= milliVolts, higher numbers represent more motor units).

  12 weeks

• Change in peroneal nerve compound muscle action potential (CMAP) at 6 weeks between treatment arms (Peroneal CMAP at 6 weeks - Peroneal CMAP at baseline 0-300mV, mV = milliVolts, higher numbers represent more motor units).

  6 weeks

• Change in peroneal nerve compound muscle action potential (CMAP) at 12 weeks between treatment arms (Peroneal CMAP at 12 weeks - Peroneal CMAP at baseline 0-300mV, mV= milliVolts, higher numbers represent more motor units).

  12 weeks

Study Arms (2)

Home Lower Extremity Strengthening

EXPERIMENTAL

Patients in this arm will undergo a 12 week strengthening program which focuses on ankle dorsi- and plantar- flexion. Clinical visits will occur at baseline, 6 weeks and 12 weeks from the start of study. At each visit all patients will undergo a clinical exam, answer questionaires and undergo MUNIX testing.

Other: Home Ankle Strengthing Program

No intervention

EXPERIMENTAL

In this portion of the study patients will not be given any intervention. Clinical visits will occur at baseline, 6 weeks and 12 weeks from the start of study. At each visit all patients will undergo a clinical exam, answer questionaires and undergo MUNIX testing of both legs.

Other: Standard of Care

Interventions

Home Ankle Strengthing Program OTHER

Patients in this arm will be given a USB or DVD video with description of ankle dorsi- and plantar- flexion resistance band exercise. They will also be given an outlined plan for there exercises, progression and an exercise diary. In general patients will start with a low resistance and low reps, over the 4 weeks they will increase the repetitions at the same resistance band. After the 4 weeks they will have the option to escalate the band resistance or continue at the same resistance and repetitions until comfortable progressing. The same 4 week progression will be used for each resistance band over the 12 weeks.

Home Lower Extremity Strengthening

Standard of Care OTHER

Patients in this arm will be directed to continue there standard care program. They will be asked to refrain from resistance exercise for 12 weeks.

No intervention

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult Patients 18 years or older with genetically confirmed CMT1A
• Adult Patients 18 years or older with a CMT1A genetically confirmed relative and a positive clinical exam or nerve conduction study consistent with CMT1A.
• Unaffected persons 18 years or older with no past medical history of peripheral neuropathy

You may not qualify if:

• Patients with a history of medical diseases that affect peripheral nerve function including diabetic neuropathy, uncontrolled thyroid dysfunction, amyloidosis, monoclonal gammopathy of uncertain significance or untreated vitamin deficiencies.
• Patients with a history of other neurologic disease which may affect peripheral nerve function or extremity strength or function including stroke, seizures with a history of Todd's paralysis, Parkinson's Disease, Dementia, Guillen-Barre Syndrome, Myasthenia Gravis, Lambert Eaton Myasthenia Gravis or hypothyroidism.
• Patients with ankle dorsiflexion strength of less than 3/5 in either limb on Medical Research Council scale.
• Patients enrolled in a clinical trial (excluding natural history studies) in the past 12 months.
• Patients who have undergone intense physical therapy, meaning more than 1 time per week for 6 or more weeks within the last 12 months.
• Patient who do resistance training of the lower extremity more than 2 times per week for more than 3 months.
• Patient in whom exercise would be consider dangerous including autonomic failure, postural orthostatic tachycardic syndrome (POTS), lower extremity deep vein thrombosis or pulmonary embolism, arterial insufficiency, uncontrolled pulmonary hypertension, uncontrolled hypertension or uncontrolled heart failure with reduced ejection fraction.

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37212, United States

Location

Related Publications (3)

• Li J. Inherited neuropathies. Semin Neurol. 2012 Jul;32(3):204-14. doi: 10.1055/s-0032-1329198. Epub 2012 Nov 1.

  PMID: 23117945 BACKGROUND

• Nandedkar SD, Barkhaus PE, Stalberg EV. Motor unit number index (MUNIX): principle, method, and findings in healthy subjects and in patients with motor neuron disease. Muscle Nerve. 2010 Nov;42(5):798-807. doi: 10.1002/mus.21824.

  PMID: 20976783 BACKGROUND

• Bas J, Delmont E, Fatehi F, Salort-Campana E, Verschueren A, Pouget J, Lefebvre MN, Grapperon AM, Attarian S. Motor unit number index correlates with disability in Charcot-Marie-Tooth disease. Clin Neurophysiol. 2018 Jul;129(7):1390-1396. doi: 10.1016/j.clinph.2018.04.359. Epub 2018 Apr 16.

  PMID: 29729594 BACKGROUND

MeSH Terms

Conditions

Charcot-Marie-Tooth Disease

Interventions

Standard of Care

Condition Hierarchy (Ancestors)

Hereditary Sensory and Motor Neuropathy; Nervous System Malformations; Nervous System Diseases; Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Polyneuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Intervention Hierarchy (Ancestors)

Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Ryan J Castoro, D.O.

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Resident Physician

Study Record Dates

• First Submitted: October 8, 2018
• First Posted: October 23, 2018
• Study Start: January 15, 2019
• Primary Completion: September 1, 2019
• Study Completion: September 1, 2019
• Last Updated: December 20, 2019

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)