PET Imaging Tau Accumulation in FTLD and Atypical Alzheimer's Using PI-2620

• Status: Not yet recruiting
• Trial end date: 2026-08-01
• Target enrollment: 0
• Participant gender: All

Summary

We will compare PI-2620 tau PET scans from patients with frontotemporal lobar degeneration (FTLD), patients with non-amnestic presentations of Alzheimer's disease (naAD), and demographically matched cognitively normal seniors.

• Phase: Phase 3
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: University of Pennsylvania
• Collaborator: National Institutes of Health (NIH)

Criteria

Inclusion Criteria:

1. Group 1: cognitively and neurologically normal seniors (CN, n=12)

a) Male or female ≥ 45 years of age currently enrolled in UNICORN (IRB #842873) b) If female, post-menopausal or surgically sterile (i.e., unable to have children due to hysterectomy, removal of the Fallopian tubes, tubal ligation, or similar surgery).

c) Cognitively and neurologically normal according to one of the following criteria:

i) Mini-Mental Status Exam (MMSE; Folstein et al., 1975) score > 27, OR ii) Montreal Cognitive Assessment (MoCA; Carson et al., 2017; Nasreddine et al., 2005) score > 25, OR iii) Global Clinical Dementia Rating of 0), OR iv) Evaluation by a trained clinician d) Not clinically depressed, according to one of the following criteria: i) Geriatric Depression scale ≤ 6 (assessed ≤ 6 months prior to study enrollment), OR ii) Evaluation by a trained clinician e) No history of early-onset neurodegenerative disease in biological siblings or parents, based on the investigators' assessment of participants' self-reported family history.

2. Group 2: non-amnestic Alzheimer's disease (naAD, n=12)

1. Male or female ≥ 45 years of age currently enrolled in UNICORN (IRB #842873)

2. If female, post-menopausal or surgically sterile (i.e., unable to have children due to hysterectomy, removal of the Fallopian tubes, tubal ligation, or similar surgery).

3. Clinically diagnosed by a trained neurologist as having logopenic-variant primary progressive aphasia (lvPPA) or posterior cortical atrophy (PCA).

4. Not clinically depressed, according to one of the following criteria:

i) Geriatric Depression scale ≤ 6 (assessed ≤ 6 months prior to study enrollment), OR ii) Evaluation by a trained clinician e) Have a study partner or legally authorized representative who can accompany the participant for all screening and study activities.

3. Group 3: FTLD due to tau (FTLD-tau, n=12)

a) Male or female ≥ 45 years of age currently enrolled in UNICORN (IRB #842873) b) If female, post-menopausal or surgically sterile (i.e., unable to have children due to hysterectomy, removal of the Fallopian tubes, tubal ligation, or similar surgery).

c) Clinically diagnosed by a trained neurologist as having progressive supranuclear palsy (PSP), non-fluent agrammatic primary progressive aphasia (naPPA), or behavioral-variant frontotemporal dementia (bvFTD) consistent with Pick's disease.

d) Not clinically depressed, according to one of the following criteria: i) Geriatric Depression scale ≤ 6 (assessed ≤ 6 months prior to study enrollment), OR ii) Evaluation by a trained clinician e) Have a study partner or legally authorized representative who can accompany the participant for all screening and study activities.

4. Group 4: FTLD due to TDP-43 (FTLD-TDP, n=12)

1. Male or female ≥ 45 years of age currently enrolled in UNICORN (IRB #842873)

2. If female, post-menopausal or surgically sterile (i.e., unable to have children due to hysterectomy, removal of the Fallopian tubes, tubal ligation, or similar surgery).

3. Clinically diagnosed by a trained neurologist as having amyotropic lateral sclerosis with frontotemporal dementia (ALS-FTD) or semantic-variant primary progressive aphasia (svPPA)

4. Not clinically depressed, according to one of the following criteria:

i) Geriatric Depression scale ≤ 6 (assessed ≤ 6 months prior to study enrollment), OR ii) Evaluation by a trained clinician e) Have a study partner or legally authorized representative who can accompany the participant for all screening and study activities.

5. Group 5: FTLD-tau due to a known genetic mutation (genetic FTLD-tau, n=3)

a) Male or female ≥ 45 years of age b) Currently enrolled in UNICORN (IRB #842873) with a genetic test result indicating a mutation in the MAPT gene.

c) If female, post-menopausal or surgically sterile (i.e., unable to have children due to hysterectomy, removal of the Fallopian tubes, tubal ligation, or similar surgery).

d) Clinically diagnosed by a trained neurologist as having progressive supranuclear palsy (PSP), non-fluent agrammatic primary progressive aphasia (naPPA), or behavioral-variant frontotemporal dementia (bvFTD) consistent with Pick's disease.

e) Not clinically depressed, according to one of the following criteria: i) Geriatric Depression scale ≤ 6 (assessed ≤ 6 months prior to study enrollment), OR ii) Evaluation by a trained clinician f) Have a study partner or legally authorized representative who can accompany the participant for all screening and study activities.

6. Group 6: FTLD-TDP due to a known genetic mutation (genetic FTLD-TDP, n=3)

a) Male or female ≥ 45 years of age b) Currently enrolled in UNICORN (IRB #842873) with a genetic test result indicating a mutation in the GRN gene or in open reading frame 72 of chromosome 9 (C9orf72).

c) If female, post-menopausal or surgically sterile (i.e., unable to have children due to hysterectomy, removal of the Fallopian tubes, tubal ligation, or similar surgery).

d) Clinically diagnosed by a trained neurologist as having amyotropic lateral sclerosis with frontotemporal dementia (ALS-FTD) or semantic-variant primary progressive aphasia (svPPA) e) Not clinically depressed, according to one of the following criteria: i) Geriatric Depression scale ≤ 6 (assessed ≤ 6 months prior to study enrollment), OR ii) Evaluation by a trained clinician f) Have a study partner or legally authorized representative who can accompany the participant for all screening and study activities.

Exclusion Criteria:

1. The participant has any medical or psychiatric conditions that, in the opinion of the investigator, would compromise the participant's safety or successful participation in the study.

2. The investigators of UNICORN (IRB #842873) have determined the participant has evidence of structural abnormalities such as major stroke or mass on MRI that is likely to interfere with analysis of the PET scan.

3. The participant is unable to tolerate or have a contraindication to imaging procedures in the opinion of an investigator.

4. The participant has a history of significant or ongoing alcohol abuse or substance abuse, or dependence based on medical record review or self-reported.

5. The participant is enrolled in a clinical trial for a treatment that targets their neurodegenerative disease.

The inclusion/exclusion criteria will be ascertained through self-report in conjunction with any medical history available through the participant's medical or research records (EPIC or the INDD database).