Clinical Trial: Effects of Botulinum Toxin Injections in Patients With Hereditary Spastic Paraplegia

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Botulinum Toxin in Patients With Hereditary Spastic Paraplegia: a Randomized, Double-blind, Placebo-controlled, Crossover Study

Brief Summary:

Hereditary spastic paraplegias constitute a heterogeneous group of diseases with the common predominant feature of spasticity of the lower limbs. The clinical picture is composed of difficulty walking, exaggerated deep reflexes, pathological reflexes such as the Babinski sign, sphincter disturbances and various degrees of weakness as well as sensory disturbances.

Spasticity is the symptom that provoques greater incapacity. Although there have been recent advances in the genetic and pathogenic characterization of SPG there is scarcity of therapeutic options. The Botulinum Toxin (BTx) is a well established treatment for movement disorders such as cervical dystonia, blepharospasm, and arm spastic following stroke.

Therefore, the investigators propose the execution of a randomized, double-blind, placebo-controlled, crossover study to evaluate the efficacy of the treatment with Btx over SPG patient's gait. The primary outcome measure will be gait velocity with the 10 meter walking test 8 weeks after injection. Each participant will be submitted to one injection session of Btx and one of placebo (consisting of sterile sodium chloride), each one separated by a period of 6 months. The primary and secondary outcomes will be evaluated by a blind investigator 8 weeks after each injection session.


Detailed Summary:

Introduction

Hereditary spastic paraplegias (SPG) constitute a heterogeneous group of diseases with a common predominant feature: spasticity of the lower limbs and difficulty walking. The neurologic examination reveals spasticity, exaggerated and pathological reflexes, such as the Babinski sign, and minor hypoesthesia. Spasticity is more evident when the patient walks than during passive movement. Weakness may or may not be present, and typically is less disabling than spasticity, especially during the initial years of the disease. The increase in tonus leads to reduced amplitude of movement and abnormal posture, altogether leading to a very slow gait, falls and articular deformities. Clinically, SPG is divided into pure and complicated forms. The first one is characterized by almost exclusive dysfunction of the pyramidal tracts. Minor sensory and sphincter disturbances are also present. The complicated subtypes encompass a wide variety of associated features such as ataxia, cognitive decline and vision loss. Genetically, SPGs are divided into autosomal dominant, autosomal recessive and X-linked forms. Pure forms are mostly inherited in an autosomal dominant manner, whereas the autosomal recessive forms mostly manifest as complicated forms. Although useful clinically, this genotype-phenotype correlation is not always true. The most used SPG classification is based on the locus that harbors the mutated gene. Each subtype is designated by the initials SPG, followed by a number that corresponds to a specific gene. The gene number is established following the chronological order of identification of each locus.

The discovery of new genes and the unraveling of molecular pathways of SPGs have lead to a better understanding of the disease in the past few years. Despite that, there are very few treatment options . There is no plac
Sponsor: University of Campinas, Brazil

Current Primary Outcome: Change from baseline in 10 meter maximum gate velocity [ Time Frame: 8 weeks after injections ]

The primary outcome measure will be change from baseline in maximum gait velocity. Each patient will be asked to walk a 10 meter distance barefooted 3 times, as fast as he can. The average velocity between the 3 trials will be used as the final measure. Assistive devices are permitted.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Change from baseline in Spastic Paraplegia Rating Scale (SPRS), [ Time Frame: 8 weeks after each procedure ]
    The same neurologist will examine the patient to evaluate change at the SPRS scale
  • Change from baseline in Ashworth spasticity scale of adductors and triceps surae muscles [ Time Frame: 8 weeks after each procedure ]
    The same neurologist will examine the patient to evaluate change from baseline
  • Change from baseline in muscle strengh (Medical Research Council scale) concerning adductors and triceps surae muscles. [ Time Frame: 8 weeks after each procedure ]
    The same neurologist will examine the patient to evaluate change from baseline
  • Change from baseline in visual analogic scale of pain [ Time Frame: 8 weeks after each procedure ]
    this scale will be applied by a neurologic physiotherapist
  • Change from baseline in brief pain inventory scale [ Time Frame: 8 weeks after each procedure ]
    this scale will be applied by a neurologic physiotherapist
  • Change from baseline in modified fatigue impact scale [ Time Frame: 8 weeks after each procedure ]
    this scale will be applied by a neurologic physiotherapist
  • Change from baseline in 10 meter comfortable walking velocity [ Time Frame: 8 weeks after each procedure ]
    this scale will be applied by a neurologic physiotherapist


Original Secondary Outcome: Same as current

Information By: University of Campinas, Brazil

Dates:
Date Received: November 9, 2015
Date Started: July 2016
Date Completion: April 2017
Last Updated: September 10, 2016
Last Verified: September 2016