SANDBOX: Scalable Assessment of Neurodegenerative Diagnosis Via Biomarkers and Online Examination
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 1,000
- 试验地点
- 12
- 主要终点
- Memory Clinic Performance Metrics
研究概览
简要总结
Dementia is a leading cause of death in the UK, and long waits for diagnosis can delay access to care and treatment. The SANDBOX study is a research study in NHS Memory Clinics investigating whether providing clinicians with additional test results could help them diagnose dementia earlier.
Adults aged 50 or over who have been referred to a Memory Clinic by their GP may be invited to take part. Taking part is voluntary and will not affect a participant's care. Participation adds to their NHS care and does not replace or delay it.
Participants complete three assessments: a blood test that measures two proteins which can indicate whether Alzheimer's-related changes may be happening in the brain (not currently available on the NHS); a genetic test for the APOE gene, which influences Alzheimer's risk; and a cognitive assessment of memory and thinking that includes a recorded speech task analysed for subtle language changes. All results are shared with the participant's clinician.
This research will help determine whether this approach can support earlier dementia diagnosis and improve care for patients across the UK.
详细描述
The SANDBOX study evaluates an approach to integrating blood-based biomarkers, APOE4 genetic testing, and digitally administered cognitive assessments into Memory Clinic diagnostic pathways. The primary aim is to assess whether this approach improves efficiency of dementia diagnosis and patient flow through Memory Clinic services.
Participants will undergo baseline assessment including venous blood draw (42.5 mL) for analysis of plasma phosphorylated tau-217, epigenetic markers in cell-free DNA, and APOE4 genotyping. Dried blood spot samples will be collected via finger-prick.
Digital cognitive testing will be conducted using CANTAB (Cambridge Neuropsychological Test Automated Battery) and recorded speech analysis.
Blood biomarker and genetic results will be withheld from clinical teams until participants have a Memory Clinic appointment scheduled, to prevent bias in triage decisions. Results will then be shared with clinicians to support diagnostic assessment. All participants will be offered genetic counseling regarding APOE4 status.
A follow-up assessment occurs at 12 months (repeat blood draws and cognitive testing). Psychological impact of genetic disclosure will be monitored using validated questionnaires (Health Anxiety Inventory, CES-D, EQ-5D-5L, IGT-AD Scale).
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
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •The participant is willing and able to provide informed consent for participation in the study, or if unable to consent, a consultee (nearest of kin or holder of Power of Attorney) is available to make a declaration.
- •Eligibility for recruitment in Scotland is restricted to participants who are able to provide informed consent themselves; participants requiring consultee consent will not be recruited in Scotland.
- •Male or female, aged 50 years or older.
- •The participant is currently on a waiting list for a participating Memory Clinic.
- •The participant lives within traveling distance to a study site.
- •The participant agrees to complete all study procedures, including genetic testing.
排除标准
- •The participant may not enter the study if any of the following criteria apply:
- •The participant has known or anticipated challenges with venous blood sampling.
- •The participant is not fluent in English.
- •The participant has a historical diagnosis of dementia.
结局指标
主要结局
Memory Clinic Performance Metrics
时间窗: From referral into the Memory Service through first Memory Clinic assessment (up to 12 months)
Time from the date of referral to the participant's Memory Clinic to the date of their first clinical assessment appointment. Reported as the mean number of days from referral to assessment.
Usability and Acceptability of Biomarker Enabled Approach-Clinician Feedback
时间窗: Every 3 months throughout the study (up to 36 months)
Clinician feedback on the usability and acceptability of the biomarker-enabled approach is assessed using a structured questionnaire. Responses are recorded using categorical Likert-type scales (e.g., Very satisfied to Very dissatisfied), scored from 1 to 5, with higher scores indicating greater satisfaction or perceived effectiveness of the triage system. We will aggregate scores into a composite overall acceptability score.
Health-Related Quality of Life (EQ-5D-5L)
时间窗: Baseline (Study Visit 1), 2 weeks after return of results (Study Visit 3), and 12 months (Study Visit 4)
Health-related quality of life measured using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L). The instrument includes five domains (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), each scored on a 5-level scale ranging from 1 (no problems) to 5 (extreme problems). Domain responses are combined into a single EQ-5D-5L index score, where higher scores indicate better health-related quality of life.
Health-Related Quality of Life - Self Rated Overall Health (EQ VAS)
时间窗: Baseline (Study Visit 1), 2 weeks after return of results (Study Visit 3), and 12 months (Study Visit 4)
Self-reported health status measured using the visual analogue scale (VAS) of the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L). The VAS ranges from 0 to 100, where 0 represents the worst health imaginable and 100 represents the best health imaginable. Higher VAS scores indicate better self-reported health status.
次要结局
- Plasma Alzheimer's Disease Biomarkers (PrecivityAD2)(Baseline (Study Visit 1) and 12 months (Study Visit 4))
- Epigenetic Biomarkers in Cell-Free DNA(Baseline (Study Visit 1), 6 months (Study Visit 4), and 12 months (Study Visit 5))
- Digital Cognitive Testing Performance (CANTAB)(Baseline (Study Visit 1), and 12 months (Study Visit 4))
- Voice-Based Biomarkers from Free Speech Analysis(Baseline (Study Visit 1), and 12 months (Study Visit 4))
- Clinical and Demographic Data(Study Visit 2, occurring at variable timepoints up to 12 months after baseline depending on clinic wait times)
- Acceptability and Feedback of Biomarker Enabled-Approach(2 weeks after return of results (Study Visit 3) and 12 months (Study Visit 4))
- Psychological impact of genetic disclosure: Assessment of Anxiety Symptoms (Health Anxiety Inventory)(Baseline (Study Visit 1), 2 weeks after return of results (Study Visit 3), and 12 months (Study Visit 4))
- Psychological impact of genetic disclosure: Assessment of Depression Symptoms (CES-D)(Baseline (Study Visit 1), 2 weeks after return of results (Study Visit 3), and 12 months (Study Visit 4))
- Genetic Risk Perception and Understanding (IGT-AD Scale)(12 months (Study Visit 4))
- Per-Patient Cost of Biomarker Enabled Approach Implementation(Throughout study duration (up to 36 months), calculated from resource utilisation data)
- Diagnostic Efficiency Compared to Standard UK Practice(Measured from baseline through Memory Clinic diagnosis (up to 12 months); compared to CPRD data throughout study duration (up to 36 months))
- Quality-Adjusted Life Years (QALYs) Gained(Study duration (up to 36 months) with health economic modeling projecting outcomes over ≥10 years)
- Cost-Effectiveness by APOE4 Carrier Status (Subgroup Analysis)(Throughout study duration (up to 36 months), with health economic modeling)
- Health Economic Model Robustness(Throughout study duration (up to 36 months), with final analysis upon study completion)
- Healthcare Resource Utilisation(Throughout study duration (up to 36 months))
研究者
Ivan Koychev
Dr Ivan Koychev
Imperial College London