Molecular Cerebral Imaging in Incipient Dementia (MCI-ID) II

NCT ID: NCT02317250

Last Updated: 2018-10-15

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE3
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-06-30
• Study Completion Date: 2022-12-31

Brief Summary

A substantial portion of people covered by Medicare will develop Alzheimer's disease and other forms of dementia that together devastate the lives of millions of people in the United States, and cost us a total of over $200 billion every year. Getting a brain scan with a PET scanner to look for abnormal brain metabolism patterns is recognized as "reasonable and necessary" for some patients with "a recently established diagnosis of dementia" (Centers for Medicare and Medicaid Services (CMS), Decision Memo CAG-00088R), but the evidence is considered less clear for patients having less severe cognitive problems, and/or for patients getting a brain scan with a PET scanner to look for abnormal proteins in the brain (CMS Decision Memo CAG-00431N). This project employs a scientifically rigorous design (prospective, multi-centered, randomized controlled trial) to determine whether such PET scanning can help distinguish more accurately than is being done in current clinical practice those patients with early molecular changes in their brains who will benefit from Alzheimer related treatments from those patients who will not, as proven by measuring to what extent the PET scans actually lead to earlier appropriate therapy, and in fact result in improved outcomes for Medicare beneficiaries and for the health care system in which they obtain care.

Detailed Description

The overarching objective of this project is to test whether diagnostic assessments informed by data on molecular cerebral changes can lead to improved health outcomes of an epidemiologically major segment of the geriatric patient population - people experiencing changes in their cognitive skills relative to their prior level of cerebral functioning. In the present proposal, we specifically aim to measure how knowledge of molecular cerebral information 1) influences the therapeutic management of patients being evaluated for symptoms of cognitive decline, and 2) impacts upon long-term health outcomes, particularly for patients having findings on positron emission tomography (PET) scans consistent with presence of Alzheimer's disease (AD)- like changes in their brains. Patients suffering from documentable decline of cognitive function will undergo baseline neuropsychologic testing, and neuroimaging with MRI and PET. Reports of PET scans will be sealed at the time of interpretation, and then randomized with respect to whether they are released to the patients' managing physicians at the time of interpretation, or two years after the time that scanning is performed. All treatment decisions will be made by the managing physicians and their patients. Cognitive abilities, functional status, and other clinical and social history parameters will be assessed every six months. Our central hypothesis is that among the group of patients whose PET scan results are conveyed to their physicians at the time of scanning, cognitive and functional abilities will be maintained at a higher level during the two years following PET. Beyond addressing the specific aims noted above and further described below, a valuable feature of this project will be the collection of a rich source of data that can be used to address many questions beyond its major focus (e.g., diagnostic value of volumetric MRI data used instead of, or in conjunction with, PET data in the Medicare beneficiary population; incremental value of applying statistically parameterizing and/or quantifying software tools to PET data). The protocol has been designed to conform to all standards specified by the Centers for Medicare and Medicaid Services (CMS) for Coverage with Evidence Development (CED), generally, and with all requirements for a CED study responsive to CMS Decision Memo CAG-00431N, specifically.

Conditions

Mild Cognitive Impairment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: TRIPLE

Study Groups

prompt amyloid imaging, delayed FDG-PET

Subject's managing physicians will be given the results of amyloid imaging scans immediately. FDG-PET results will be released two years after scanning.

Group Type: EXPERIMENTAL

Amyloid imaging

Intervention Type: PROCEDURE

Amyloid imaging brain scans are administered once to all arms.

FDG-PET

Intervention Type: PROCEDURE

\[F-18\] FDG-PET brain scans are administered once to all arms.

prompt FDG-PET, delayed amyloid imaging

Subject's managing physicians will be given the results of FDG-PET scans immediately. Amyloid imaging results will be released two years after scanning.

Group Type: EXPERIMENTAL

Amyloid imaging

Intervention Type: PROCEDURE

Amyloid imaging brain scans are administered once to all arms.

FDG-PET

Intervention Type: PROCEDURE

\[F-18\] FDG-PET brain scans are administered once to all arms.

prompt FDG-PET, prompt amyloid imaging

Both FDG-PET and amyloid imaging scan results will be made immediately available to the managing physician.

Group Type: EXPERIMENTAL

Amyloid imaging

Intervention Type: PROCEDURE

Amyloid imaging brain scans are administered once to all arms.

FDG-PET

Intervention Type: PROCEDURE

\[F-18\] FDG-PET brain scans are administered once to all arms.

delayed FDG-PET, delayed amyloid imaging

Neither FDG-PET nor amyloid imaging scan results will be released to the managing physician for 2 years.

Group Type: ACTIVE_COMPARATOR

Amyloid imaging

Intervention Type: PROCEDURE

Amyloid imaging brain scans are administered once to all arms.

FDG-PET

Intervention Type: PROCEDURE

\[F-18\] FDG-PET brain scans are administered once to all arms.

Interventions

Amyloid imaging

Amyloid imaging brain scans are administered once to all arms.

Intervention Type: PROCEDURE

FDG-PET

\[F-18\] FDG-PET brain scans are administered once to all arms.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

1. Cognitive decline and/or personality change is present, as observable by physician and/or close contact(s) of the patient; or in the absence of this, the patient provides a clear history of decline that the patient's physician deems to be reliable.

2. If history or neurologic exam reveals findings suspicious for stroke, tumor, bleed, ictal activity, or hydrocephalus, then CT/MRI and appropriate neurological or neurosurgical consultation must have been obtained.

3. Standard history, physical, and laboratory screen have been performed to identify possible presence of depression, substance abuse, malnourishment, medication effects and interactions, cardiopulmonary compromise, electrolyte/calcium imbalance, anemia, hypoxemia, infection, thyroid dysfunction, renal dysfunction, hepatic dysfunction, or glucose dysregulation.

4. Any positive findings revealed in 2) or 3) above have been appropriately treated, wherever possible, but cognitive/behavioral deficit persists post-therapy.

Exclusion Criteria

1. Subjects under age 65 will not be recruited, in order to enhance the relevance of the project by focusing on the group of Medicare beneficiaries in whom serious concerns about early signs and symptoms of senile onset dementia are most typically emerging.

2. Cognitive dysfunction has impaired subject's ability to perform activities of daily living.

3. Present or past history of thyroid disease.

4. Claustrophobia or metal in body or other condition that would preclude PET or MRI from being acquired.

5. Visual, auditory or motor deficits that would preclude accurate neuropsychological testing.

6. AD-specific pharmacotherapy already initiated.

• Minimum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centers for Medicare and Medicaid Services

FED

Sponsor Role: collaborator

University of California, Los Angeles

OTHER

Sponsor Role: lead

Responsible Party

Daniel H. Silverman

Professor, Medical and Molecular Pharmacology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Daniel Silverman, MD, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of California, Los Angeles

Other Identifiers

11-00815-02

Identifier Type: -

Identifier Source: org_study_id