LIFE-DSR-Biomarker Sub-study of Biomarkers in Down Syndrome Related Alzheimer's Disease (DS-AD)

NCT ID: NCT06860373

Last Updated: 2025-03-06

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 5 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-27
• Study Completion Date: 2024-04-17

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).

Conditions

Down Syndrome

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

Radiotracer [18F]MK-6240

In this sub-study, participants will have two \[18F\]MK-6240 tau PET scans. Participants will undergo administration of \[18F\]MK-6240 to detect the presence of tau in the brain. The applied \[18F\]MK-6240 radioactive dose will be approximately 5 mCi (185 MBq) ± 20%. The mass dose will not exceed 20 µg. This is the only arm.

Group Type: OTHER

[18F]MK-6240

Intervention Type: BIOLOGICAL

\[18F\]MK-6240 will be synthesized, purified, and formulated at the local radiochemistry synthesis laboratory and will be administered as a sterile, pyrogen-free solution by IV injection.

Interventions

[18F]MK-6240

\[18F\]MK-6240 will be synthesized, purified, and formulated at the local radiochemistry synthesis laboratory and will be administered as a sterile, pyrogen-free solution by IV injection.

Intervention Type: BIOLOGICAL

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.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 55 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

LuMind IDSC Foundation

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Barrow Neurological Institute

Phoenix, Arizona, United States

Countries

United States

Other Identifiers

LIFE-DSR-BIO DS-AD

Identifier Type: -

Identifier Source: org_study_id