Clinical trial NCT06844734: A Prospective Cohort Study of ITB Treatment for HSP
Official title: Intrathecal Baclofen for the Management of Hereditary Spastic Paraparesis: a Prospective Cohort Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Hereditary Spastic Paraplegia
Keywords: Hereditary Spastic Paraparesis
Intrathecal baclofen
Lead sponsor: Shanghai 6th People's Hospital
Sponsor class: OTHER
First posted: 2025-02-25
Enrollment: 50
Sex: ALL
Minimum age (years): 14
Maximum age (years): 70
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Six-Minute Walk Test(6-MWT)
timeFrame: From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
measure: Step length
timeFrame: From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
measure: walking speed
timeFrame: From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
measure: knee flexion angle
timeFrame: From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
measure: Modified Ashworth Scale(MAS)
timeFrame: From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
measure: Range of Motion (ROM) of Joints
timeFrame: From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
Secondary outcomes:
measure: Patient Global Impression of Change (PGIC) scale
timeFrame: From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
measure: Oswestry Disability Index (ODI)
timeFrame: From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
measure: Numeric Rating Scale (NRS)
timeFrame: From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
measure: MMSE score
timeFrame: From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
measure: MoCA score
timeFrame: From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
measure: SDS
timeFrame: From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
measure: SAS
timeFrame: From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
measure: SPRS score
timeFrame: From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
measure: Complications
timeFrame: From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
measure: GMFM-88
timeFrame: From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
measure: GAS
timeFrame: From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
measure: Foot deformity molding
timeFrame: From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
measure: Scoliosis assessment
timeFrame: From the end of treatment to observations at 6 months, 12months, 18months, 24months, 30months, and 36months respectively
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Shanghai Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine
state: Shanghai
Study officials:
affiliation: Shanghai Sixth People's Hospital affiliated to Shanghai Jiao Tong University School Of Medicine
name: Li Cao, phD
role: PRINCIPAL_INVESTIGATOR
References: