Studying the Prodromal and Early Phase of Hereditary Spastic Paraplegia Type 4 (SPG4)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 1
- 主要终点
- Identification of a change of recognizable signs or symptoms
研究概览
简要总结
Study goals
- Prospective longitudinal data on progression in the natural course of SPG4 in presymptomatic mutation carriers prior to clinical disease onset and in early stages of disease
- Biomarkers providing objective measures of disease activity
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- Triple (Participant, Care Provider, Investigator)
盲法说明
Two Arms are blinded (mutation carriers vs. non mutation carriers) the third arm is an open-arm for presymptomatic tested mutation carriers
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •First degree relatives (parents, offspring, and sibs) of SPG4 patients or symptomatic individuals with known SPAST mutation
- •Age 18 to 70 years
- •Written, informed consent (patient)
排除标准
- •No known SPAST-mutation within the family
- •Manifest spastic gait (subclinical signs like increased deep tendon reflexes, positive Babinski sign are allowed)
- •Participation in interventional trials
研究组 & 干预措施
Mutation carrier
The participants will be tested genetically if they carry a disease causing mutation or not. Depending on their genetic test result they will at the end of the study divided into two groups. The clinician will be blinded throughout the entire study to the genetic results.
干预措施: SPRS Score and clinical signs (Other)
Mutation carrier
The participants will be tested genetically if they carry a disease causing mutation or not. Depending on their genetic test result they will at the end of the study divided into two groups. The clinician will be blinded throughout the entire study to the genetic results.
干预措施: Cognition Testing using CANTAB (Behavioral)
Mutation carrier
The participants will be tested genetically if they carry a disease causing mutation or not. Depending on their genetic test result they will at the end of the study divided into two groups. The clinician will be blinded throughout the entire study to the genetic results.
干预措施: Lumbar Puncture and blood draw (Diagnostic Test)
Mutation carrier
The participants will be tested genetically if they carry a disease causing mutation or not. Depending on their genetic test result they will at the end of the study divided into two groups. The clinician will be blinded throughout the entire study to the genetic results.
干预措施: MRI (Diagnostic Test)
Mutation carrier
The participants will be tested genetically if they carry a disease causing mutation or not. Depending on their genetic test result they will at the end of the study divided into two groups. The clinician will be blinded throughout the entire study to the genetic results.
干预措施: Electrophysiology (Diagnostic Test)
Mutation carrier
The participants will be tested genetically if they carry a disease causing mutation or not. Depending on their genetic test result they will at the end of the study divided into two groups. The clinician will be blinded throughout the entire study to the genetic results.
干预措施: Testing functional performance (Diagnostic Test)
Mutation carrier
The participants will be tested genetically if they carry a disease causing mutation or not. Depending on their genetic test result they will at the end of the study divided into two groups. The clinician will be blinded throughout the entire study to the genetic results.
干预措施: Non motor symptoms (Diagnostic Test)
Non-mutation carrier
The participants will be tested genetically if they carry a disease causing mutation or not. Depending on their genetic test result they will at the end of the study divided into two groups. The clinician will be blinded throughout the entire study to the genetic results.
干预措施: SPRS Score and clinical signs (Other)
Non-mutation carrier
The participants will be tested genetically if they carry a disease causing mutation or not. Depending on their genetic test result they will at the end of the study divided into two groups. The clinician will be blinded throughout the entire study to the genetic results.
干预措施: Cognition Testing using CANTAB (Behavioral)
Non-mutation carrier
The participants will be tested genetically if they carry a disease causing mutation or not. Depending on their genetic test result they will at the end of the study divided into two groups. The clinician will be blinded throughout the entire study to the genetic results.
干预措施: Lumbar Puncture and blood draw (Diagnostic Test)
Non-mutation carrier
The participants will be tested genetically if they carry a disease causing mutation or not. Depending on their genetic test result they will at the end of the study divided into two groups. The clinician will be blinded throughout the entire study to the genetic results.
干预措施: MRI (Diagnostic Test)
Non-mutation carrier
The participants will be tested genetically if they carry a disease causing mutation or not. Depending on their genetic test result they will at the end of the study divided into two groups. The clinician will be blinded throughout the entire study to the genetic results.
干预措施: Electrophysiology (Diagnostic Test)
Non-mutation carrier
The participants will be tested genetically if they carry a disease causing mutation or not. Depending on their genetic test result they will at the end of the study divided into two groups. The clinician will be blinded throughout the entire study to the genetic results.
干预措施: Testing functional performance (Diagnostic Test)
Non-mutation carrier
The participants will be tested genetically if they carry a disease causing mutation or not. Depending on their genetic test result they will at the end of the study divided into two groups. The clinician will be blinded throughout the entire study to the genetic results.
干预措施: Non motor symptoms (Diagnostic Test)
Known-mutation carriers but presymptomatic
In a third arm (open arm) we will also include positive predictive tested participants which know that they are carrying a known mutation but are at inclusion into the study asymptomatic (according to the inclusion / exclusion criteria).
干预措施: SPRS Score and clinical signs (Other)
Known-mutation carriers but presymptomatic
In a third arm (open arm) we will also include positive predictive tested participants which know that they are carrying a known mutation but are at inclusion into the study asymptomatic (according to the inclusion / exclusion criteria).
干预措施: Cognition Testing using CANTAB (Behavioral)
Known-mutation carriers but presymptomatic
In a third arm (open arm) we will also include positive predictive tested participants which know that they are carrying a known mutation but are at inclusion into the study asymptomatic (according to the inclusion / exclusion criteria).
干预措施: Lumbar Puncture and blood draw (Diagnostic Test)
Known-mutation carriers but presymptomatic
In a third arm (open arm) we will also include positive predictive tested participants which know that they are carrying a known mutation but are at inclusion into the study asymptomatic (according to the inclusion / exclusion criteria).
干预措施: MRI (Diagnostic Test)
Known-mutation carriers but presymptomatic
In a third arm (open arm) we will also include positive predictive tested participants which know that they are carrying a known mutation but are at inclusion into the study asymptomatic (according to the inclusion / exclusion criteria).
干预措施: Electrophysiology (Diagnostic Test)
Known-mutation carriers but presymptomatic
In a third arm (open arm) we will also include positive predictive tested participants which know that they are carrying a known mutation but are at inclusion into the study asymptomatic (according to the inclusion / exclusion criteria).
干预措施: Testing functional performance (Diagnostic Test)
Known-mutation carriers but presymptomatic
In a third arm (open arm) we will also include positive predictive tested participants which know that they are carrying a known mutation but are at inclusion into the study asymptomatic (according to the inclusion / exclusion criteria).
干预措施: Non motor symptoms (Diagnostic Test)
结局指标
主要结局
Identification of a change of recognizable signs or symptoms
时间窗: every two years, up to eight years
Identification of recognizable signs or symptoms and their time course prior to disease-onset defined by the presence of a spastic gait and at least one of three additional features: 1. manifest spasticity in the clinical examination (Ashworth Scale \>0) 2. positive Babinski sign 3. pyramidal pattern of muscle weakness (e.g. hip abduction or foot elevation preferentially involved)
次要结局
- Cognition (MoCA)(every two years, up to eight years)
- MRI (not obligate) - DTI(every two years, up to eight years)
- MRI (not obligate) - volumetry(every two years, up to eight years)
- Nfl(every two years, up to eight years)
- Subclinical progression (10m walking time)(every two years, up to eight years)
- Subclinical progression (5-stair climbing test time)(every two years, up to eight years)
- Subclinical progression (3 minute walking test (3MW))(every two years, up to eight years)
- Non-motor symptoms (quality of life)(every two years, up to eight years)
- Non-motor symptoms (fatigue)(every two years, up to eight years)
- Non-motor symptoms (pain)(every two years, up to eight years)
- Non-motor symptoms (restless-legs)(every two years, up to eight years)
- Cognition (CANTAB)(every two years, up to eight years)
- Non-motor symptoms (SPRS inventory V3)(every two years, up to eight years)
- Non-motor symptoms (depression)(every two years, up to eight years)
- SPRS(every two years, up to eight years)
研究者
Prof. Dr. Ludger Schöls
Prinicipal Investigator
University Hospital Tuebingen