Pathophysiology of Neurodegeneration in Late-life Depression (AV45+THK)

NCT03430869 | Completed Phase 2

• 1 other identifier: 201601655A0
• Study Type: interventional
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

Late-life depression has been frequently associated with cognitive impairment. Several meta-analyses consistently suggested that a history of depression approximately doubles an individual's risk for developing dementia later in life. Neurodegeneration may play an important component in late-life depression. The pathophysiology behind the link between late-life depression and the subsequent development of dementia largely remains unclear, and should be heterogeneous. This highlights the need to identify specific neurodegenerative pathways involved in late-life depression, which will facilitate research on mechanisms and new treatments in the future. The recently published the National Institute on Aging and the Alzheimer Association (NIA-AA) criteria might provide new insights and frameworks to explore the patterns of neurodegenerative process in elderly depressed patients and to categorize them into different biomarker-based groups. In the present project, the investigators will recruit 40 patients with lifetime major depressive disorder, and 20 non-depressed cognitively normal comparison subjects. Alzheimer's disease pathology (A) was determined by measuring Aβ deposition by F-18 AV-45 PET, and neurodegeneration (N) was established by measuring hippocampal volume using MRI. Individuals were categorised as A-N-, A+N-, A+N+, or suspected non-Alzheimer's disease pathophysiology (A-N+, SNAP). All subjects will further undergo F-18-THK-5351 image study to detect underlying tau pathology. By doing this, the investigators will elucidate the neurodegenerative pathophysiology behind the link between depressive disorder and the subsequent development of dementia.

Conditions

Major Depressive Disorder

Keywords

late-life depression; major depressive disorder; Alzheimer's disease dementia; neurodegeneration; amyloid plague, tau protein

Outcome Measures

Primary Outcomes (1)

• The standard uptake value ratio (SUVR) of 18F-florbetapir

  The primary outcome is to measure the standard uptake value ratio (SUVR) of 18F-florbetapir in patients with major depressive disorder and compare the difference between patients and non-depressed subjects. 18F-florbetapir SUVRs of each volume of interest are analyzed using whole the cerebellum as the reference region.

  three years

Secondary Outcomes (1)

• The standard uptake value ratio (SUVR) of 18F-THK-5351

  three years

Study Arms (2)

F-18 AV-45

EXPERIMENTAL

F-18 AV-45 imaging

Drug: F-18 AV-45

F-18-THK-5351

EXPERIMENTAL

F-18-THK-5351 imaging

Drug: F-18-THK-5351

Interventions

F-18 AV-45 DRUG

In the present project, the investigators will recruit 40 patients with lifetime major depressive disorder, and 20 non-depressed cognitively normal comparison subjects. Alzheimer's disease pathology (A) was determined by measuring Aβ deposition by F-18 AV-45 PET.

F-18 AV-45

F-18-THK-5351 DRUG

In the present project, the investigators will recruit 40 patients with lifetime major depressive disorder, and 20 non-depressed cognitively normal comparison subjects. All subjects will further undergo F-18-THK-5351 image study to detect underlying tau pathology. By doing this, the investigators will elucidate the neurodegenerative pathophysiology behind the link between depressive disorder and the subsequent development of dementia.

F-18-THK-5351

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Enrolled subjects will be 50 to 90 years of age. They should understand the content of consent and sign consent after the explanation of the benefits and possible side effects of this trial
• Patients with a clinical diagnosis of major depressive disorder according to the DSM -5 criteria (APA, 2013).
• Comparison subjects evaluated for lifetime absence of psychiatric illness by MINI interview (Sheehan et al., 1998).
• Fertile females must avoid becoming pregnant and must use adequate contraceptive methods for 30 days after administration of study radiotracer.

You may not qualify if:

• Any subject has clinically definite diagnosis of dementia before study recruitment according to the NIA-AA criteria for possible or probable clinically-defined AD dementia ( McKhann, 2011) or the DSM -5 criteria for any type of dementia (APA, 2013).
• Any subject has clinically significant or unstable medical diseases including metabolic, renal, liver, lung or cardiovascular disorders including metabolic, renal, liver, lung or cardiovascular disorders
• Any subject has a current or past history of clinically significant neurological insults affecting brain structure or function like completed stroke, head injury or epilepsy
• Any subject has current alcohol or other substances abuse and/ or dependence within the recent one year, or previously prolonged history of substances abuse
• Any females who is pregnant or lactating
• Any subjects with history of severe allergic or anaphylactic reactions particularly to the study medication, or any subjects who are recognized as high risk of adverse effects by principle investigator.

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead

Study Sites (1)

Chang Gung Memorial Hospital

Taoyuan District, Guishan, 333, Taiwan

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Nerve Degeneration; Frontotemporal Dementia

Interventions

florbetapir

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Frontotemporal Lobar Degeneration; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases; Neurocognitive Disorders

Study Officials

• KUAN YI WU

  Attending physician

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 20, 2017
• First Posted: February 13, 2018
• Study Start: March 23, 2018
• Primary Completion: December 28, 2021
• Study Completion: December 31, 2021
• Last Updated: January 26, 2022

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)