Spinal Cord Stimulation Therapy for Hereditary Spastic Paraplegias Patients

Effects of Spinal Cord Stimulation Therapy on Motor Function and Gait in Patients With Pure Hereditary Spastic Paraplegias

It's a single-center, prospective, open label clinical study with a 12 months follow-up period, to investigate the therapeutic effect and safety of spinal cord stimulation (SCS) on motor function and gait in patients with pure Hereditary Spastic Paraplegias.

Study Overview

• Status: Recruiting
• Conditions: Gait; Motor Function
• Intervention / Treatment: Procedure: Spinal cord stimulation

Detailed Description

Pure hereditary spastic paraplegia is a heterogeneous group of genetic disorders characterized by degeneration of the corticospinal tracts, coursing with progressive weakness and spasticity of the lower limbs. The available anti spastic agents and surgical procedures involving anti-spastic systemic drugs, botulinum toxin, intrathecal baclofen, and even selective dorsal rhizotomy have not shown an improvement in muscle strength. Physical rehabilitation alone has shown positive results in short term, but this effect tends to fade away in few months.To date, there are no effective treatments for progressive deficits or disease-modifying therapy for Hereditary spastic paraplegia patients,

Spinal cord stimulation is a wellestablished therapy for the treatment of chronic neuropathic pain. Recently, some pilot studies demonstrated encouraging results of SCS in improving motor function. Patients severely affected by spinal cord injury experienced enhancements in leg movements and Parkinson's disease, primary progressive freezing of gait, and multiple system atrophy with predominant parkinsonism patients improved gait performance and freezing of gait after spinal cord stimulation by inducing changes in spinal and brain circuitry function. Some case studies suggest spinal cord stimulation may delay motor worsening and be innovative lines of research for the treatment of spastic paraplegia. However, evidence from larger numbers of subjects is still lacking. The objective of this study is to investigate the therapeutic effect and safety of spinal cord stimulation on motor function and gait in patients with pure hereditary spastic paraplegias

It's a single-center, prospective, open label clinical study with a 12 months follow- up period. The intended study population is individuals suffering from pure hereditary spastic paraplegia.Each participant will complete an enrollment/ screening/baseline visit, a spinal cord stimulation implant and activation visit, and a minimum of two follow-up visits, including visit at 3 months and the final study visit at 12months. The participants will proceed to implantation after satisfying implant inclusion and exclusion criteria. Paddle-shaped Spinal cord stimulation electrode with 16 contacts ((AdaptiveStim 39, 565; Medtronic, Minneapolis, USA) will be implanted into the epidural space at the thoracic levels ranging from T10 to T12. Electrode position will be verified by X-ray. The stimulators will be turned on within 1 month after electrode implantation surgery (slightly below sensory threshold). The stimulation parameters could vary freely, but medications will be kept constant during the study period. At the end of month 12, participants will enter the long-term follow-up in which medications and stimulation parameters could vary freely.

• Study Type: Interventional
• Enrollment (Anticipated): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100053
      • Recruiting
      • Xuanwu Hospital，Capital Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 70 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. aged between 14 and 70 years
2. patients with pure hereditary spastic paraplegias
3. with progressive weakness and spasticity of the lower limbs, and the gait dysfunction treatable by medication but not adequately controlled with medications
4. Understand potential risk/benefit, consent to the study, study procedures, and agree to complete the study follow-up visits and comply with the study protocol requirements.

Exclusion Criteria:

1. cognitive impairment ( MMSE≤24), depression (HAMD>24),acute psychosis, active alcohol or drug abuse, terminal illness, and any major medical or psychological histories, diagnoses, conditions, or comorbidities that would interfere with participation in the study per the investigatior's medical judgment
2. surgical or medical contraindications to spinal cord stimulation surgery(e.g. uncontrolled hypertension, advanced coronary artery disease).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Spinal cord stimulation therapy; Spinal cord stimulation at the thoracic levels ranging from T10 to T12.	Procedure: Spinal cord stimulation; Paddle-shaped Spinal cord stimulation electrode with 16 contacts (AdaptiveStim® 39, 565;Medtronic, USA) will be implanted into the epidural space at the thoracic levels ranging from T10 to T12.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in spastic paraplegia rating scale(SPRS)	demonstrate the statistically significant improvement in score of spastic paraplegia rating scale(SPRS) from baseline( Off medication) to 12 months(On stimulation/Off medication); The score of SPRS ranges from 0 to 52, higher scores mean a worse outcome .	twelve months after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
change in the score of Modified Ashworth Scale	demonstrate statistically significant improvement in score of Modified Ashworth Scale from baseline( Off medication) to 12 months(On stimulation/Off medication); The score of Modified Ashworth Scale ranges from 0 to 4, higher scores mean a worse outcome.	twelve months after surgery
change in Activities of Daily Living Scale (ADL)	demonstrate statistically significant improvement in score of Activities of Daily Living Scale (ADL) from baseline to 12 months. The score of ADL ranges from 0 to 100, higher scores mean a better outcome.	twelve months after surgery
change in Tinetti Balance and Gait Analysis	demonstrate statistically significant improvement in the score of Tinetti balance and gait analysis from baseline( Off medication) to 12 months(On stimulation/Off medication); The score of Tinetti balance and gait ranges from 0 to 28, higher scores mean a better outcome.	twelve months after surgery
change in Berg Balance Scale(BBS)	demonstrate statistically significant improvement in score of Berg Balance Scale(BBS) from baseline( Off medication) to On stimulation/Off medication state at 12 months. BBS ranged from 0 to 56, higher scores mean a better outcome.	twelve months after surgery
Clinical Global Impression-Global Improvement	Evaluations will performed in off-stimulation and in on-stimulation conditions at 12 months after surgery on the basis of the physician's assessment, as well as on the basis of the patients'selfreported satisfaction. It is rated on a 7-point scale, range from 1(very much improved) through to 7 (very much worse)	twelve months after surgery

Collaborators and Investigators

• Sponsor: Xuanwu Hospital, Beijing
• Investigators: Principal Investigator: Yuqing Zhang, MD, Xuanwu Hospital, Beijing

Study record dates

Study Major Dates

• Study Start (Actual): November 15, 2021
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2023

Study Registration Dates

• First Submitted: December 2, 2021
• First Submitted That Met QC Criteria: January 6, 2022
• First Posted (Actual): January 19, 2022

Study Record Updates

• Last Update Posted (Actual): January 19, 2022
• Last Update Submitted That Met QC Criteria: January 6, 2022
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Keywords: gait; spinal cord stimulation; Spasticity; Hereditary Spastic Paraplegias
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Congenital Abnormalities; Genetic Diseases, Inborn; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Peripheral Nervous System Diseases; Neuromuscular Manifestations; Heredodegenerative Disorders, Nervous System; Nervous System Malformations; Paralysis; Muscle Hypertonia; Polyneuropathies; Hereditary Sensory and Motor Neuropathy; Muscle Spasticity; Paraplegia; Spastic Paraplegia, Hereditary
• Other Study ID Numbers: 20211116

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes