Clinical trial NCT06860373: LIFE-DSR-Biomarker Sub-study of Biomarkers in Down Syndrome Related Alzheimer's Disease (DS-AD)
Official title: LIFE-DSR-Biomarker Sub-study of Biomarkers in Down Syndrome Related Alzheimer's Disease (DS-AD)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Down Syndrome
Lead sponsor: LuMind IDSC Foundation
Sponsor class: OTHER
First posted: 2025-03-06
Enrollment: 5
Sex: ALL
Minimum age (years): 35
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: This is an optional sub-study that will enroll participants from the LIFE-DSR parent protocol. Participants will undergo assessments at two timepoints, including: additional blood samples for PBMC and RNA extraction, as well as a lumbar puncture for collection of CSF, and/or MRI and tau PET imaging. Sub-study visits will be scheduled around a similar calendar-day as the parent protocol study visits (e.g., Month (M) 0 (M0) and M16, or M16 and M32).

Detailed description: This is an optional sub-study that will enroll participants from the LIFE-DSR parent protocol. Participants will undergo assessments at two timepoints, including: additional blood samples for PBMC and RNA extraction, as well as a lumbar puncture for collection of CSF, and/or MRI and tau PET imaging. Sub-study visits will be scheduled around a similar calendar-day as the parent protocol study visits (e.g., Month (M) 0 (M0) and M16, or M16 and M32).

The aim is to increase knowledge of biomarkers of interest in DS-AD clinical progression and perform deep immunophenotyping of PBMC samples. Intervention studies in people with DS depend upon determining the optimal age for treatments to be given, by identifying or developing reliable outcome measures that are most sensitive to decline and discovering biomarkers most closely related to disease progression.

For tau deposition, the aim of this study is to ascertain the degree and distribution of tau pathology in DS as a function of age using tau PET, and to determine the longitudinal progression of that pathology. As such, enrichment of the study population included in the tau PET sub-study for presence of tau PET positive scans, and in particular tau PET scans in the earliest stages of positivity, is desirable. Accomplishing this may require flexibility in recruitment, including adjustments of age eligibility as a response to emerging new information in the sub-study population as the study proceeds. PET images will be reviewed in near real-time to enable adaption of the age strata based on the presence or absence of tau PET signal.

All the above endpoints will be acquired with informed consent and assent. All data is intended for research purposes only and associated clinical data will be stored securely.

Participants will have the option to participate in:

* LP to collect CSF and venipuncture to collect a blood sample OR
* Imaging (MRI and tau PET) and venipuncture to collect a blood sample OR
* Both

  * LP to collect CSF and venipuncture to collect a blood sample AND
  * Imaging (MRI and tau PET).

Eligibility criteria: Inclusion Criteria:

1. The participant must be currently enrolled in the LIFE-DSR parent protocol.
2. The adult with DS must be age 35 to 55 years.
3. Both the participant, or LAR, and their caregiver must be able to understand and be willing to provide consent. The LAR will sign the informed consent. The participant will sign the informed consent or assent.
4. Both the participant, or LAR, and their caregiver must be willing to comply with the scheduled visits and scheduled assessments.
5. Agreement of caregiver and clinician the participant can cooperate with protocol tasks.

Exclusion Criteria:

Participants meeting any of these criteria are excluded from the LP portion of the sub-study.

1. Assessment (per medical history, physical exam, vital signs or other clinically relevant measure or circumstance) which, in the opinion of the site PI, makes the participant unsuitable for participation in this study.
2. Evidence for raised intracranial pressure. Examples include papilledema on physical exam or CNS lesion with mass effect.
3. Presence of lower spinal malformations, prior lumbosacral spinal surgery, local infection, or other abnormalities that would exclude lumbar puncture.
4. Allergy to Lidocaine (xylocaine) or its derivatives.
5. Evidence or history of significant active bleeding or coagulation disorder, or use of anticoagulant medications such as coumadin, heparin, thrombin inhibitors (e.g., dabigatran) or factor Xa inhibitors (e.g., apixaban).
6. Previous or ongoing treatment with aducanumab (AduhelmTM) OR any anti-amyloid OR any anti-tau antibody OR investigational treatment within the previous 30-calendar days of this sub-study baseline LP. Treatment with AduhelmTM is permitted in the LIFE-DSR parent protocol but precludes participation in this LP sub-study.

   Participants meeting any of these criteria are excluded from the imaging portion of the sub-study.
7. Contraindication to MRI or PET scans, evidenced by presence or history of any significant or uncontrolled medical condition which, in the opinion of the Investigator, would increase the potential risk to the study participant (e.g., history of CNS infection, history of exposure to CNS toxin, epilepsy, sensitivity to flashing lights, pacemaker).
8. Participants in whom MRI is contraindicated including, but not limited to, those with a pacemaker, presence of metallic fragments near the eyes or spinal cord or cochlear implant. Dental fillings do not present a risk for MRI.
9. Suffers from claustrophobia, inability to tolerate confined spaces, or prior failed experience completing MRI scans or blood draws.
10. Positive pregnancy test or currently breast-feeding.
11. Previous or ongoing treatment with aducanumab (AduhelmTM) OR any anti-amyloid OR any anti-tau antibody OR investigational treatment within the previous 30-calendar days of this sub-study baseline PET. Treatment with AduhelmTM is permitted in the LIFE-DSR parent protocol but precludes participation in this imaging sub-study.

Primary outcomes:
measure: Primary Outcome Measure to establish a biobank specifically for DS participants
timeFrame: Month 0 and Month 16 or Month 16 and Month 32
measure: Primary Outcome to ascertain the degree and distribution of tau pathology in DS as a function of age using tau PET
timeFrame: Month 0 and Month 16 or Month 16 and Month 32
Secondary outcomes:
measure: Secondary Outcome is to increase knowledge of biomarkers of interest in DS-AD clinical progression and perform deep immunophenotyping of PBMC and plasma samples.
timeFrame: Month 0 and Month 16 or Month 16 and Month 32
Other outcomes:
measure: Exploratory Outcome - Biomarkers Comparisons
timeFrame: through study completion, an average of 2 years
Locations:
city: Phoenix
country: United States
facility: Barrow Neurological Institute
state: Arizona
Study officials:
References: