A Prospective Cohort Study of ITB Treatment for HSP (ITB-HSP)

Intrathecal Baclofen for the Management of Hereditary Spastic Paraparesis: a Prospective Cohort Study

The investigators conduct a prospective cohort study to explore the treatment effectiveness of continuous infusion of intrathecal baclofen (ITB) for hereditary spastic paraplegia (HSP) in China, delve into the optimal timing for starting treatment, and investigate the response differences among different subtypes. The ultimate goal is to provide clinical evidence and guidance for the application of ITB in treating HSP in China, as well as improve the life expectancy and quality of life for HSP patients. The main questions it aims to answer are:

1. Changes in gait and motor function, as well as spasticity levels, compared to pre-surgery and control group after ITB surgery.
2. Changes in quality of life, pain, psychological and emotional status, and cognition compared to pre-surgery and control group after ITB surgery.
3. Complications following ITB surgery.
4. Impact of ITB surgery on the occurrence and progression of skeletal deformities.
5. Subgroup analysis: comparing surgical outcomes between different genotypes and between simple versus complex types.
6. Determine the optimal timing for ITB intervention.

Study Overview

• Status: Recruiting
• Conditions: Hereditary Spastic Paraplegia

Detailed Description

Hereditary spastic paraplegias (HSPs) are a heterogeneous group of neurodegenerative disorders characterized by progressive spasticity and weakness of the lower limbs due to retrograde axonal degeneration of the corticospinal tract. Baclofen is a selective GABA-B receptor agonist and is commonly used for the treatment of spasticity. Baclofen can be administered orally or intrathecally by the surgical implantation of a specialized pump. Intrathecal baclofen (ITB) is significantly more potent for the treatment of spasticity than the oral form. The goal of this clinical trial is to explore the efficacy and safety of ITB in the treatment of HSP patients. This study is prospective, open-label, single center, and this trial will last for 3 years. A total of 50 patients will participate. Twenty-five patients who will receive ITB and the other 25 control patients will receive oral baclofen. Patients with HSP aged 14 to 70 years, with a Modified Ashworth Scale score of ≥3 in ≥2 joints of lower limb, will be recruited. Patients who do not agree to undergo ITB and/or those who have an inadequate response during intrathecal baclofen test will receive oral baclofen therapy and undergo natural history observation. Professional clinical evaluations are conducted regularly for both groups.

• Study Type: Observational
• Enrollment (Estimated): 50

Contacts and Locations

• Study Contact: Name: Li Cao, phD; Phone Number: +86 21 64369263; Email: caoli2000@yeah.net
• Study Contact Backup: Name: Wotu Tian, phD; Phone Number: +86 21 64369181; Email: wotu_tian@163.com

Study Locations

• China
  • Shanghai
    • Shanghai, Shanghai, China, 213000
      • Recruiting
      • Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
      • Contact: Wotu Tian, phD; Phone Number: 21 64369181; Email: wotu_tian@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients meet the clinical and genetic diagnostic criteria of hereditary spastic paraplegia (HSP) between 14 to 70 years old with of lower limbs. Participants suffered from severe spasticity with score ≥ 3 by Modified Ashworth assessment in ≥2 joints of lower limbs. Patients agree to participate in clinical trials and able to understand and comply with the research program.

Description

Inclusion Criteria:

• Patients meet the clinical and genetic diagnostic criteria of hereditary spastic paraplegia (HSP);
• Age: 14 to 70 years old
• Modified Ashworth Score for lower limbs: ≥2 joints with muscle tone ≥grade 3
• Patients are willing to participate in clinical trials and able to understand and comply with the research program

Exclusion Criteria:

• Patients are allergic to the baclofen
• Other neurological diseases likely affecting the evaluation of study treatment
• Other medical conditions such as: heart disease, tumor, blood disease, liver disease, kidney disease, etc. in the past 1 year
• Pregnancy or lactating women or subjects who are unable to use appropriate contraception during the trial
• Participating in another study drug trial and used the investigational drug in the past 30 days
• Subjects have poor compliance or other factors that are not suitable for participating in the clinical trial

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Intrathecal baclofen management of hereditary spastic paraparesis; Patients with hereditary spastic paraparesis aged 14 to 70 years, with a Modified Ashworth Scale score of greater or equal to 3 in 2 or more joints of lower limb, and agree to undergo Intrathecal baclofen surgery will be recruited. Patients will receive professional assessment every six months.
The oral baclofen group; Patients who do not agree to intrathecal baclofen treatment or those who do not achieve satisfactory therapeutic effect during the baclofen testing phase will be included in oral baclofen group. Patients will receive professional assessment every six months, with natural history observation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Six-Minute Walk Test(6-MWT)	The 6-MWT measures the distance a person can walk in six minutes. A shorter distance indicates lower exercise capacity.	From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
Step length	Step length is measured by gait analysis device. Step length refers to the distance from the heel strike of one foot to the heel strike of the opposite foot. Longer step length indicates that the patient has improved lower limb muscle strength and coordination, and that spastic symptoms have been alleviated.	From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
walking speed	Walking speed is measured by gait analysis device. Walking speed refers to the distance covered by a person within a unit of time while walking, expressed in meters per minute (m/min). An increase in walking speed indicates an improvement in spasticity and motor function.	From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
knee flexion angle	Knee flexion angle is measured by gait analysis device.An increase in the knee flexion angle indicates improved motor function and reduced spasticity.	From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
Modified Ashworth Scale(MAS)	range: 0-4, higher scores mean more severe spasticity.	From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
Range of Motion (ROM) of Joints	ROM refers to the distance and direction a joint can move to its full potential. Flexion, extension, abduction, adduction of joints are measured.	From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Global Impression of Change (PGIC) scale	range (1-7), lower scores mean a better outcome	From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
Oswestry Disability Index (ODI)	The ODI consists of 10 sections (items). Each section is scored on a scale of 0 to 5, with higher scores indicating greater levels of disability.	From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
Numeric Rating Scale (NRS)	rang 0 to 10, higher scores mean a worse outcome	From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
MMSE score	Mini-Mental State Examination (MMSE) : range: 0-30, higher scores mean a better outcome	From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
MoCA score	Montreal Cognitive Assessment (MoCA) score: range: 0-30, higher scores mean a better outcome.	From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
SDS	Self-Rating Depression Scale: Index score < 50 Normal range; 50-59 Mild depression; 60-69 Moderate depression; ≥70 Severe depression	From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
SAS	Self-Rating Anxiety Scale (SAS): 20-44 Normal range; 45-59 Mild to moderate anxiety levels; 60-74 Marked to severe anxiety levels; 75 and above Extreme anxiety levels	From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
SPRS score	The change in the Spastic Paraplegia Rating Scale (SPRS) score : range: 0-52, higher scores mean a worse outcome	From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
Complications	Catheter breakage, blockage, infection, etc.	From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
GMFM-88	Gross Motor Function Measure-88 (GMFM-88) score: range: 0-264, higher scores mean a better outcome	From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
GAS	Goal Attainment Scale (GAS) - Family Goal Selection Version: range: -2-+2, higher scores mean a better outcome	From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
Foot deformity molding	Utilizing CT digital 3D reconstruction technology	From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
Scoliosis assessment	Measurement of the Cobb angle using spinal X-ray imaging	From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively

Collaborators and Investigators

• Sponsor: Shanghai 6th People's Hospital
• Investigators: Principal Investigator: Li Cao, phD, Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: February 10, 2025
• First Submitted That Met QC Criteria: February 19, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: February 24, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Intrathecal baclofen; Hereditary Spastic Paraparesis
• Additional Relevant MeSH Terms: Neurologic Manifestations; Musculoskeletal Diseases; Nervous System Diseases; Muscular Diseases; Muscle Hypertonia; Neuromuscular Manifestations; Neuromuscular Diseases; Genetic Diseases, Inborn; Peripheral Nervous System Diseases; Neurodegenerative Diseases; Congenital Abnormalities; Heredodegenerative Disorders, Nervous System; Nervous System Malformations; Polyneuropathies; Paralysis; Hereditary Sensory and Motor Neuropathy; Muscle Spasticity; Paraplegia; Spastic Paraplegia, Hereditary
• Other Study ID Numbers: 2024-KY-305(K)

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.: No