proTmedula- Temporal Profile of Potential Molecular Determinants of Spinal Cord Injury Rehabilitation and Regeneration
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 106
- 试验地点
- 1
- 主要终点
- Molecular/cellular candidate biomarkers with a strong association to functional independence
研究概览
简要总结
This study main aim is to identify molecular determinants of better recovery following spinal cord injury (SCI), as biomarkers of neurological and/or functional improvement and a proxy for neuroregeneration. For that, omics analyses of several biological samples will be performed, to comprehensively portray the molecular and cellular profiles of the patients with SCI at key time points of the pathology: pre-rehabilitation, post-rehabilitation and one-year post-injury. The main question it aims to answer is: 'Are there specific molecules (and related biological pathways) that impact the functional recovery of spinal cord injury patients during the subacute phase, in a way that future targeted pharmacological or genetic interventions may improve SCI outcomes?'.
详细描述
BACKGROUND:
Spinal cord injury (SCI) is a devastating condition with no effective cure, that hinders motor, sensory and autonomic functions. Besides affecting the spinal cord parenchyma, SCI has various systemic impacts including altered metabolic states, chronic inflammation, gastrointestinal alterations like gut dysbiosis, and urinary dysfunctions. Given these systemic pathophysiological effects, and the physiological drainage of molecules from the cerebrospinal fluid into the bloodstream, SCI biomarkers may also be identified in the blood/serum, urine and feces.
This study hypothesizes that alterations in proteins, metabolites and gut bacteria from blood/serum, urine and/or feces, reflect and influence neurological and/or functional recovery of SCI patients. Thus, using high-throughput omics analyses, the investigators here aim to identify molecular determinants and microbiota taxa that correlate with clinical recovery measures (the motor scores assessed by the International Standards for Neurological Classification of Spinal Cord Injury - ISNCSCI, the American Spinal Injury Association (ASIA) Impairment Scale - AIS grades, the Spinal Cord Independence Measure - SCIM-IV, and the Functional Independence Measure - FIM). In parallel, the investigators also aim to monitor potential neuroregeneration-associated molecules identified in pre-clinical studies led by the investigators, such as project GoBack (New therapeutic targets for spinal cord injury regeneration - PTDC/CVT-CVT/32261/2017), project pAGE (Protein aggregation across the lifespan - CENTRO-01-0145-FEDER-000003), project MEDISIS (CENTRO-01-0246-FEDER-000018), and project ReConnect (Developing innovative therapies for spinal cord injury - COMPETE2030-FEDER-00891600).
STUDY OBJECTIVES:
This research work has the following main objectives:
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Clinically diagnosed with traumatic spinal cord injury
- •Adults (≥18 years).
- •Injury occurred less than 6 months ago (subacute phase).
- •Classification A-D in The American Spinal Injury Association (ASIA) Impairment Scale (AIS).
- •Any neurological level of injury.
排除标准
- •Use of probiotics one-month prior admission.
- •Use of immunomodulatory drugs one-month prior admission.
- •Major gastrointestinal surgery in the last five years.
- •Active gastrointestinal diseases.
- •Other CNS diseases (besides SCI).
研究组 & 干预措施
Able-bodied controls
Age, sex and body mass index-matched control group of participants recruited among able-bodied personnel from Centro de Reabilitação do Norte, Unidade Local de Saúde de Gaia e Espinho, E.P.E. or their relatives, without any known CNS disease.
SCI cohort
Spinal cord injury patients admitted for hospitalization at Centro de Reabilitação do Norte, Unidade Local de Saúde de Gaia e Espinho, E.P.E. categorized into two subgroups: with A or B (motor complete injuries) classification, or with C or D (motor incomplete) classification in The American Spinal Injury Association (ASIA) Impairment Scale (AIS).
结局指标
主要结局
Molecular/cellular candidate biomarkers with a strong association to functional independence
时间窗: From admission into the rehabilitation hospital (~2 months post-injury) until discharge (~4 months post-injury)
Association between functional independence, assessed by the Spinal Cord Independence Measure, 4th version (SCIM IV), and by the Functional Independence Measure (FIM), with levels of specific molecular or cellular candidate biomarkers. Association studies will consider functional independence measures (at admission, their variation, and/or at discharge) and specific molecular or cellular candidate biomarkers, such as protein or bacterial levels (at admission, their variation, and/or at discharge).
Molecular/cellular candidate biomarkers with a strong association to neuromotor impairment
时间窗: From admission into the rehabilitation hospital (~2 months post-injury) until discharge (~4 months post-injury)
Association between total motor scores, assessed by the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI), with levels of specific molecular or cellular candidate biomarkers. Association studies will consider ISNCSCI motor scores (at admission, their variation, and/or at discharge) and specific molecular or cellular candidate biomarkers, such as protein or bacterial levels (at admission, their variation, and/or at discharge).
次要结局
- Molecular/cellular candidate biomarkers identified in the primary outcome measures with a strong association to neurological impairment(From admission into the rehabilitation hospital (~2 months post-injury), across discharge (~4 months post-injury), and until follow-up (1-year post-injury))
- Longitudinal profiles of key molecules (and bacteria) across post-intensive inpatient rehabilitation, and a period post-discharge (subacute and chronic phases)(From admission into the rehabilitation hospital (~2 months post-injury), across discharge (~4 months post-injury), and until follow-up (1-year post-injury))
研究者
Prof. Sandra Vieira
Prof. Sandra I. Vieira
Aveiro University