TreatHSP/SPAX Master Protocol: Adaptive Platform for Longitudinal Progression, Biomarkers and Pathophysiology in Ataxias, Hereditary Spastic Paraplegias and Spastic Ataxias (TreatHSP/SPAX)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 4,000
- 试验地点
- 30
- 主要终点
- Modified Spastic Paraplegia Rating Scale
研究概览
简要总结
Ataxias, hereditary spastic paraplegias (HSP), and spastic ataxias (collectively referred to as SPAX diseases) are rare neurological conditions that cause progressive problems with walking, balance, coordination, and daily activities. Although many SPAX diseases are caused by specific genetic changes, there is still limited knowledge about how symptoms develop over time, how fast the diseases progress, and which clinical or biological measures best reflect meaningful changes for patients.
The TreatHSP Master Protocol establishes an adaptive natural history study platform designed to improve the understanding of SPAX diseases across all ages and disease stages. Within this platform, the TreatHSP/SPAX study serves as the core natural history study, providing a shared framework for long-term clinical follow-up, standardized outcome assessments, and biosample collection.
Participants enrolled in TreatHSP/SPAX are followed over time to document disease progression using clinical examinations, patient- and caregiver-reported outcomes, digital movement measures, imaging, and biological samples. In addition to this core dataset, the TreatHSP Platform allows optional, disease- or hypothesis-specific substudies to be added over time in selected participant groups. These additional assessments are introduced under the same master protocol, without creating separate stand-alone studies.
The overall goal of the TreatHSP Master Protocol is to generate high-quality natural history data, identify sensitive and patient-relevant outcome measures, and support the development of future therapies for ataxias, hereditary spastic paraplegias, and spastic ataxias.
详细描述
Overview and Objectives: The TreatHSP Protocol defines an adaptive observational study platform for natural history research, outcome development, and biomarker discovery in ataxias, hereditary spastic paraplegias (HSP), and spastic ataxias (SPAX diseases). The platform is designed to support longitudinal, regulatory-grade data collection across genetically and clinically heterogeneous rare neurological disorders.
Within the TreatHSP platform, TreatHSP/SPAX represents the core natural history study. All participants are enrolled into TreatHSP/SPAX and undergo a standardized set of core assessments, forming the backbone of the platform. Additional disease- or hypothesis-specific investigations may be conducted within the same platform framework.
The primary objectives of the TreatHSP platform are to:
Characterize the longitudinal clinical course of SPAX diseases across genotypes, ages, and disease stages.
Identify, develop, and validate patient-relevant clinical outcome assessments. Discover and validate molecular, imaging, digital, and functional biomarkers relevant for disease progression, prognosis, and therapy development.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 5 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •General inclusion criteria:
- •- Age 5 or older
- •Cohort 1: Affected
- •Clinical diagnosis of neurodevelopmental or neurodegenerative ataxia, spastic ataxia, HSP or related phenotype AND
- •Alternative causes of phenotype excluded
- •Cohort 2: Presymptomatic mutation carriers
- •- Premanifest mutation carrier of (likely) pathogenic variant(s) in a disease gene associated with ataxia, spastic ataxia, HSP or related phenotype
- •Cohort 3: Family controls - 1st or 2nd degree relative of a person with a clinical or genetic diagnosis of ataxia, spastic ataxia, HSP or related phenotype
- •Cohort 4: Community controls
- •- Healthy individual unrelated to a person with neurodevelopmental or neurodegenerative ataxia, spastic ataxia, HSP or related phenotype
排除标准
- •Presence of an alternative neurological or systemic condition that sufficiently explains the phenotype and is incompatible with ataxia, spastic ataxia, hereditary spastic paraplegia, or a related disorder.
- •Severe comorbidity or unstable medical condition that substantially interferes with study participation or interpretation of neurological and functional assessments.
- •Inability to comply with study procedures or follow-up requirements.
- •Lack of informed consent, including absence of consent by a legally authorized representative where required.
- •Current participation in an interventional clinical trial that may interfere with the objectives or outcome assessments of this observational study.
研究组 & 干预措施
Family control
1st or 2nd degree relative of a person with a clinical or genetic diagnosis of ataxia, spastic ataxia, HSP or related phenotype (group: Affected)
Community control
Healthy individual unrelated to a person with neurodevelopmental or neurodegenerative ataxia, spastic ataxia, HSP or related phenotype
Affected
Clinical diagnosis of neurodevelopmental or neurodegenerative ataxia, spastic ataxia, HSP and alternative cause of phenotype excluded
Presymptomatic mutation carrier
Premanifest mutation carrier of (likely) pathogenic variant(s) in a disease gene associated with ataxia, spastic ataxia, HSP or related phenotype
结局指标
主要结局
Modified Spastic Paraplegia Rating Scale
时间窗: Through study completion, an average of 5 years, measured annually
The modified Spastic Paraplegia Rating Scale (mSPRS) is a clinician-reported outcome measure assessing disease severity in hereditary spastic paraplegia and related spastic movement disorders. It evaluates functional mobility, spasticity, muscle strength, pain and bladder function. The mSPRS is adapted from the original Spastic Paraplegia Rating Scale to improve feasibility and sensitivity to change in longitudinal studies. It can be applied in individuals aged 5 years and older, with higher scores indicating greater disease severity. The mSPRS serves as the primary outcome measure for the assessment of disease severity in all participants with hereditary spastic paraplegia.
Scale for the Assessment and Rating of Ataxia (SARA)
时间窗: Through study completion, an average of 5 years, measured annually
The Scale for the Assessment and Rating of Ataxia (SARA) is a standardized clinician-reported outcome measure used to quantify the severity of ataxia. It assesses key domains including gait, stance, sitting, speech disturbance, limb coordination, and fine motor control. The SARA provides a global measure of ataxia-related motor impairment and is widely used in both clinical practice and longitudinal research studies. The SARA is applied in study participants aged 8 years and older, with higher scores indicating greater ataxia severity. The SARA serves as the primary outcome measure for the assessment of disease severity in all participants with ataxia.
SPAX Composite Scale (SPAXCOM)
时间窗: Through study completion, an average of 5 years, measured annually
SPAXCOM is a clinician-reported composite outcome measure developed to assess disease severity in individuals with spastic ataxia. It integrates key motor and functional domains relevant to spastic-ataxic phenotypes, including gait and balance, coordination, spasticity, and functional mobility. SPAXCOM is designed to capture the combined contribution of pyramidal and cerebellar dysfunction and to provide a sensitive measure of disease severity and progression in spastic ataxia. Higher scores indicate greater disease severity. SPAXCOM serves as the primary outcome measure for participants with spastic ataxia.
次要结局
- Friedreich Ataxia Rating Scale - Activities of Daily Living (FARS-ADL)(Through study completion, an average of 5 years, measured annually)
- Inventory of Non-Ataxia Signs - PLUS (INAS-PLUS)(Through study completion, an average of 5 years, measured annually)
- MRC Sum Score for Muscle Strength(Through study completion, an average of 5 years, measured annually)
- TreatHSP Quality of Life (TreatHSP-QoL)(Through study completion, an average of 5 years, measured annually)
- Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD)(Through study completion, an average of 5 years, measured annually)
研究者
Rebecca Schuele
Director, Division of Neurodegenerative Diseases | Department of Neurology
University Hospital Heidelberg