Diagnostic Test for Alzheimer's Disease

(DTAD Trial)

Not currently recruiting at 2 trial locations

Overseen By Wendy Qiu, MD PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Boston University

Must not be taking: Insulin, Pramlintide, GLP-1, others

Disqualifiers: Diabetes, Stroke, Seizures, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

What You Need to Know Before You Apply

What is the purpose of this trial?

The trial aims to develop a simple blood test for early detection of Alzheimer's disease (AD). It involves a single injection of Pramlintide, a drug typically used for diabetes, to help detect proteins linked with AD in the blood. The trial includes three groups: individuals with mild memory issues, those with probable AD, and healthy individuals without memory problems. It seeks participants who have memory concerns or a diagnosis of probable Alzheimer's and are patients at specific research centers. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking advancements in Alzheimer's detection.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications, specifically insulin, pramlintide, other injectable anti-diabetic drugs, and oral anti-diabetic products. If you are on any of these, you would need to discontinue them to participate.

What prior data suggests that this diagnostic test is safe?

Research shows that Pramlintide, a medication similar to a natural hormone, is generally safe for people without diabetes. In earlier studies, participants who received a single injection of Pramlintide experienced no major safety issues. Pramlintide already has FDA approval for treating diabetes, indicating its safety is well understood. However, studies found that long-term use of Pramlintide can increase certain proteins in the brains of mice. While this might not affect a one-time dose, researchers remain cautious. Overall, Pramlintide appears safe for short-term use, but anyone considering joining a trial should discuss potential risks with their doctor. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about the pramlintide challenge test for Alzheimer's disease because it offers a fresh approach to diagnosing this condition. Unlike traditional methods that primarily rely on cognitive testing and imaging, pramlintide is administered to challenge the brain and observe its response, potentially revealing early signs of Alzheimer's disease. This approach could lead to earlier and more accurate diagnosis, which is crucial for managing and treating the disease effectively. Additionally, pramlintide's mechanism may uncover new insights into the disease process itself, possibly paving the way for novel therapeutic strategies.

What evidence suggests that this diagnostic test is effective for early detection of Alzheimer's disease?

Research has shown that Pramlintide, a drug initially used for diabetes, might aid in early detection of Alzheimer's disease. In studies with Alzheimer's patients and mice, a single injection of Pramlintide facilitated the passage of substances between the brain and the blood. This process allowed amyloid-beta proteins, associated with Alzheimer's, to move from the brain into the blood. The increase of these proteins in the blood could help measure their levels in the brain. In this trial, participants from various groups, including those with probable Alzheimer's disease, amnestic mild cognitive impairment, and normal cognition, will undergo the pramlintide challenge test to assess its effectiveness in early Alzheimer's detection. If successful, this method could represent a significant breakthrough in diagnosing and treating the disease. ^{1 2 6 7 8}

Who Is on the Research Team?

Wendy Qiu, MD PhD

Principal Investigator

Boston Medical Center and BUSM

Are You a Good Fit for This Trial?

This trial is for individuals with mild cognitive impairment or Alzheimer's, who are part of certain research centers and have a BMI between 20-35. Participants must not have diabetes, recent infections, history of stroke or brain injury, seizures, or use related medications. Those with probable AD need confirmed pathology and a designated proxy.

Inclusion Criteria

Probable AD subjects must be confirmed for positive AD pathology in the CNS

Probable AD subjects must have a designated research proxy signed before they became demented.

Current research subjects at the BU ADC, VA BHS, or IU ADC

Exclusion Criteria

I have had a brain injury with loss of consciousness.

Unexplained hypoglycemia (glucose ≤ 60 mg/dL) or hyperglycemia (glucose ≥ 126 mg/dL) pre-injection

I have diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pramlintide Challenge Test

Participants receive a single injection of Pramlintide to assess blood-brain barrier permeability and measure plasma Aβ levels

1 day

1 visit (in-person)

Immediate Monitoring

Plasma Aβ and t-tau changes, as well as plasma inflammatory and metabolic changes, are measured at multiple time points after the challenge test

180 minutes

1 visit (in-person)

Follow-up

Participants are monitored for changes in cognitive and biomarker outcomes at 12 and 24 months post challenge

24 months

2 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Pramlintide

Trial Overview Researchers are testing a blood-based diagnostic test for early Alzheimer's detection using Pramlintide. This drug may allow Amyloidbeta peptides to move from the brain into the blood after injection, potentially indicating brain amyloid levels.

How Is the Trial Designed?

Group I: Probable AD Experimental Treatment 1 Intervention

Participants with probable AD with positive imaging AD pathology will receive the pramlintide challenge test.

Group II: Amnestic MCI Active Control 1 Intervention

Participants with amnestic MCI with or without positive AD imaging pathology will receive the pramlintide challenge test.

Group III: Control- Normal Cognition Active Control 1 Intervention

Participants with normal cognition without any memory complaints will receive the pramlintide challenge test.

Who Is Running the Clinical Trial?

Boston University

Lead Sponsor

Trials

494

Recruited

9,998,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Published Research Related to This Trial

The ideal biomarker for Alzheimer's disease should have over 80% sensitivity and specificity, be non-invasive, and validated through multiple independent studies, ensuring reliability and reproducibility.

For early-onset familial Alzheimer's, mutations in specific genes (presenilin 1, presenilin 2, and amyloid precursor protein) are key indicators, while in late-onset cases, the presence of the apolipoprotein E e4 allele and cerebrospinal fluid levels of Abeta42 and tau are more relevant for diagnosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Consensus report of the Working Group on: "Molecular and Biochemical Markers of Alzheimer's Disease". The Ronald and Nancy Reagan Research Institute of the Alzheimer's Association and the National Institute on Aging Working Group. [2022]

Current diagnostic tests for Alzheimer's disease (AD) are improving early diagnosis, but definitive diagnosis still relies on autopsy findings of amyloid plaques and neurofibrillary tangles.

Research is focusing on developing less invasive peripheral biomarkers from skin or blood samples, which may offer high sensitivity and specificity for diagnosing AD and tracking its progression, addressing limitations of cerebrospinal fluid (CSF) biomarkers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peripheral biomarkers of Alzheimer's disease. Khan, TK., Alkon, DL.[2015]

A new biochemical test called Aβ-PMCA can detect misfolded Aβ oligomers in cerebrospinal fluid, which are crucial in the development of Alzheimer's disease, with a sensitivity of 90% and specificity of 92%.

This method can differentiate Alzheimer's patients from those with other neurodegenerative or neurological disorders, providing a promising approach for early and accurate diagnosis of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection of misfolded Aβ oligomers for sensitive biochemical diagnosis of Alzheimer's disease. Salvadores, N., Shahnawaz, M., Scarpini, E., et al.[2022]

In a study involving 771 participants over 18 months, a decrease in the ratio of plasma Aβ1-42 to Aβ1-40 was found in patients with Alzheimer's disease, indicating a potential biomarker for early diagnosis.

Plasma Aβ1-42 levels also decreased in individuals with mild cognitive impairment and those transitioning from healthy to mild cognitive impairment, suggesting that monitoring these levels could help track disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Changes in plasma amyloid beta in a longitudinal study of aging and Alzheimer's disease. Rembach, A., Faux, NG., Watt, AD., et al.[2022]

Identifying biomarkers for Alzheimer's disease (AD) could lead to more accurate and less invasive diagnoses, moving beyond the traditional reliance on autopsy evaluations.

Promising fluid and imaging biomarkers have been discovered that may help detect preclinical AD, allowing for earlier intervention and better predictions of disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biomarkers of Alzheimer's disease. Craig-Schapiro, R., Fagan, AM., Holtzman, DM.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5956916/

Pramlintide: the effects of a single drug injection on blood ... Studies suggest that a single injection of pramlintide, an amylin analog, induces changes in Alzheimer's disease (AD) biomarkers in the blood of AD mouse ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5424531/

An amylin analog used as a challenge test for Alzheimer's ... Pramlintide use appeared to be safe in the absence of diabetes. The biomarker changes as a result of the pramlintide challenge, which distinguished AD from ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT03560960

Multi-Center Development of a Novel Diagnostic Test for ... If successful for use as an early AD biomarker (i.e., at the Mild Cognitive Impairment (MCI) stage), this could be a game-changer for both early AD diagnostics ...

4. trialx.com trialx.com/clinical-trials/listings/221223/multi-center-development-of-a-novel-diagnostic-test-for-alzheimers-disease/

Multi-Center Development of a Novel Diagnostic Test for ... If Pramlintide is effective in releasing mobile pools of Aß from the brain into the blood, this could also have some therapeutic potential, with ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0197458013005290

Neuroprotective effects of the amylin analogue pramlintide ... Pramlintide administration improved performance in the novel object recognition task, a validated test of memory and cognition. The pramlintide-treated mice had ...

6. jamanetwork.com jamanetwork.com/journals/jamanetworkopen/fullarticle/2748598

Association of Plasma Amylin Concentration With ... An extremely high concentration of plasma amylin, which may lead to amylin aggregation and loss of its protective function for the brain, may be a risk factor ...

7. nature.com nature.com/articles/s41598-020-60664-5

Amylin and pramlintide modulate γ-secretase level and ... Our findings showed that thirty days of intraperitoneal injection with amylin or pramlintide increased Aβ burden in mice brains. Mechanistic ...

8. sciencedirect.com sciencedirect.com/topics/neuroscience/pramlintide

Pramlintide - an overview | ScienceDirect Topics Pramlintide is an injectable amylin analogue used as an adjunct to insulin treatment in type 1 and type 2 diabetes.