Pilot PET Study of Regional Cerebral Protein Synthesis in Alzheimer's

Terminated

• Conditions: Alzheimer Disease
• Interventions: Diagnostic Test: [C11] Leucine PET scan; Diagnostic Test: [18F] Flutemetamol PET scan; Diagnostic Test: MRI scan

• Registration Number: NCT05491902
• Lead Sponsor: University of Manchester

Brief Summary

Measuring the rate of cerebral protein synthesis (rCPS) may enable us to better-understand the progression of Alzheimer's Disease (AD). This study is using a new method of measuring rCPS non-invasively, and to offer new approaches to the assessment of new therapeutic strategies in clinical trials.

Previous studies have established the utility of \[11C\]-Leucine PET to assess the rCPS. This study will use \[11C\]- Leucine PET to measure rCPS in AD patients versus age-matched and young healthy subjects to determine whether a measurable difference exists.

The study will involve participants receiving up to two PET scans, a structural MRI scan. The PET scanning procedures will involve some withdrawal of blood samples.

The ultimate goal of this proposal is to indicate new routes for treatment of AD.

Detailed Description

Not available

Study Timeline

• Study Start: 2017-10-09
• Primary Completion: 2020-10-15
• Study Completion: 2020-10-15
• Study First Submitted: 2021-09-28
• Status Verified: 2022-08
• Study First Submitted QC: 2022-08-05
• Last Update Submitted: 2022-08-05
• Study First Posted: 2022-08-08
• Last Update Posted: 2022-08-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 10

Inclusion Criteria

Not provided

Exclusion Criteria

• Have a history of or a current clinically significant neurologic or psychiatric disease (other than AD);
• Have a current clinically significant endocrine or metabolic disease, pulmonary, renal or hepatic impairment, or cancer;
• Have a clinically significant infectious disease, including Acquired Immunodeficiency Syndrome (AIDS) or Human Immunodeficiency Virus (HIV) infection;
• Have a recent history of alcohol or substance abuse or dependence;
• Clinically significant brain injury or abnormality, other than associated with AD;
• Are women of childbearing potential who are not surgically sterile, not refraining from sexual activity, or not using reliable methods of contraception (as detailed in Section 7.5.1);
• Treatment with stable doses of psychotropic medication is not prohibited. In particular, patients with AD may be on a stable dose of an anticholinesterase, memantine, neuroleptic or antidepressant, and may be taking vitamin E at the time of imaging;
• Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of Gilbert's syndrome or asymptomatic gallstones);
• History of or suffers from claustrophobia or participant feels unable to lie flat and still on their back for a period of up to 90 minutes in the PET scanner;
• Previous inclusion in a research and/or medical protocol involving nuclear medicine, PET or radiological investigations or occupational exposure in the past 12 months or greater than 10 mSv in a single year including the proposed study. Clinical exposure from which the participant receives a direct benefit is not included in these calculations;
• Previous inclusion in a research and/or medical protocol involving study medication within the last 3 months;
• In the opinion of the study team they are unlikely to comply with the study protocol and restrictions that it imposes. ;
• Contraindications for participants undergoing an MRI scan (including but not limited to metal implants pacemakers, etc.).

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Early onset mild to moderate AD	[18F] Flutemetamol PET scan	Patients aged 50 to 69
Early onset mild to moderate AD	MRI scan	Patients aged 50 to 69
Late onset mild to moderate AD	[18F] Flutemetamol PET scan	Patients aged 70 and above
Older Healthy Volunteer	[C11] Leucine PET scan	Aged 50 to 69
Early onset mild to moderate AD	[C11] Leucine PET scan	Patients aged 50 to 69
Late onset mild to moderate AD	MRI scan	Patients aged 70 and above
Older Healthy Volunteer	[18F] Flutemetamol PET scan	Aged 50 to 69
Older Healthy Volunteer	MRI scan	Aged 50 to 69
Younger Healthy Volunteer	[C11] Leucine PET scan	Aged 18 - 25
Younger Healthy Volunteer	MRI scan	Aged 18 - 25

Primary Outcome Measures

Name	Time	Method
Regional changes in Protein Synthesis Rate in AD brain compared to age-matched controls	2 years after completion of patient recruitment	A primary outcome of this study will be to determine if regional changes in PSR, as measured by \[11C\]-Leucine PET, in early onset AD brain are lower compared to age-matched controls. The output parameter used to determine this will be derived from the most appropriate PET pharmacokinetic model for this ligand in human.
Regional changes in Protein Synthesis Rate in healthy controls	2 years after completion of patient recruitment	Comparison of any regional changes in PSR from the CNS of young healthy controls with older healthy controls, will occur, to assess if there is an age-dependent decline in PSR in healthy human brain and whether its regional distribution is different from disease-related changes.

Secondary Outcome Measures

Name	Time	Method
Regional changes in Protein Synthesis Rate in AD patients	2 years after completion of patient recruitment	Comparison of any regional changes in PSR from the CNS of early onset AD patients compared with late onset AD patients.Assessment of amyloid deposition effect on rCPS.

Trial Locations

Locations (2)

Wolfson Molecular Imaging Centre (University of Manchester); 🇬🇧 Manchester, United Kingdom

Salford Royal NHS Foundation Trust; 🇬🇧 Manchester, United Kingdom