Alzheimer DiseaseNCT05491902

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

An observational study of Alzheimer Disease, run by University of Manchester at 2 sites in United Kingdom.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Trial 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. Read more about this study

Who is it for?: Ages 18 years and olderHealthy volunteers can take part
Conditions the study is for: Alzheimer Disease
What is being tested?: [C11] Leucine PET scan, [18F] Flutemetamol PET scan and MRI scan
Type of treatment: Injection or infusion
How many people: 10 participants
Where: 2 sitesUnited Kingdom
Study dates: 9 Oct 2017to 15 Oct 2020
Phase: Observational
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
Healthy volunteers accepted
Adult, Older adult

Study population: Up to 12 AD participants will be recruited by the Salford Royal Foundation Trust in collaboration with clinical partners in appropriate clinical services for dementia. Up to 12 healthy controls will be recruited by approaching spouses and carers of patients or through the "Join Dementia Research" and "Citizen Scientist Salford" networks.

Who may be able to join

Patients may be included in the early onset probable AD group if they:
Are males or females between 50 and 69 years of age, inclusive, with onset of symptoms before age 65;
Meet the clinical criteria of the National Institute on Aging and the Alzheimer's Association workgroup for probable AD [25]. They have a significant cognitive impairment, Mini Mental State Examination (MMSE) score between 10 and 24 inclusive. Imaging biomarkers (hippocampal volume and cortical amyloid deposition) will be recorded for exploratory correlational analysis with PSR, but will not be used as criteria for inclusion;
Have a caregiver who can report on their mental status and activities of daily
living (ADL);
Must have capacity and be able to give informed consent.

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Willing to comply with protocol and lifestyle restrictions;
Are women of childbearing potential in whom pregnancy or breast feeding has been excluded by a standard questionnaire (Appendix 3).
Understanding of English (for questionnaires);
Participant is ambulant and capable of attending a PET scan visit as an outpatient;
Participants with female partners of child-bearing potential must agree to use one of the contraception methods listed in Protocol Section 7.5.1. This criterion must be followed from after the first PET scan until after the follow-up contact;
Adequate collateral flow to the radial and ulnar arteries in both hands as determined by an Allen's test;
Body weight ≥ 50 kg.
Patients may be included in the late onset probable AD group if they:
Are males or females ≥70 years of age with onset of symptoms not before age 65;
Meet the clinical criteria of the National Institute on Aging and the Alzheimer's Association workgroup for probable AD [25]. They have a significant memory impairment, Mini Mental State Examination (MMSE) score between 10 and 24 inclusive. Imaging biomarkers (hippocampal volume and cortical amyloid deposition) will be recorded for exploratory correlational analysis with PSR, but will not be used as criteria for inclusion;
Have a caregiver who can report on their mental status and activities of daily living (ADL);
Must have capacity and be able to give informed consent.
Willing to comply with protocol and lifestyle restrictions;
Are women of childbearing potential in whom pregnancy or breast feeding has been excluded by a standard questionnaire (appendix).Understanding of English (for questionnaires);
Participant is ambulant and capable of attending a PET scan visit as an outpatient;
Participants with female partners of child-bearing potential must agree to use one of the contraception methods listed in Section 7.5.1. This criterion must be followed from after the first PET scan until after the follow-up contact;
Adequate collateral flow to the radial and ulnar arteries in both hands as determined by an Allen's test;
Body weight ≥ 50 kg.
Subjects may be included in the older control group if they:
Are males or females between 50 and 69 years of age, inclusive;
Do not have a history of or a current clinically significant neurologic or psychiatric disease and do not have symptoms of cognitive impairment
Have a Mini Mental State Examination (MMSE) score at screening between 27 and 30, and perform normally on a memory test including delay recall memory;
Willing to comply with protocol and lifestyle restrictions;
Are women of childbearing potential in whom pregnancy or breast feeding has been excluded by a standard questionnaire (appendix).Understanding of English (for questionnaires);
Participant is ambulant and capable of attending a PET scan visit as an outpatient;
Participants with female partners of child-bearing potential must agree to use one of the contraception methods listed in Section 7.5.1. This criterion must be followed from after the first PET scan until after the follow-up contact;
Adequate collateral flow to the radial and ulnar arteries in both hands as determined by an Allen's test;
Body weight ≥ 50 kg.
Subjects may be included in the young control group if they:
Are males or females between 18 and 25 years of age, inclusive;
Do not have a history of or a current clinically significant neurologic or psychiatric disease and do not have symptoms of cognitive impairment;
Do not have a first grade relative with early onset AD;
Have a Mini Mental State Examination (MMSE) score at screening between
27 and 30, and perform normally on a memory test including delay recall memory;
Willing to comply with protocol and lifestyle restrictions;
Are women of childbearing potential in whom pregnancy or breast feeding has been excluded by a standard questionnaire (appendix).Understanding of English (for questionnaires);
Participant is ambulant and capable of attending a PET scan visit as an outpatient;
Participants with female partners of child-bearing potential must agree to use one of the contraception methods listed in Section 7.5.1. This criterion must be followed from after the first PET scan until after the follow-up contact;
Adequate collateral flow to the radial and ulnar arteries in both hands as determined by an Allen's test;
Body weight ≥ 50 kg.

Who cannot join

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);

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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.).

Trial locations and contacts

2 sites in 1 country.

United Kingdom2 sites

Wolfson Molecular Imaging Centre (University of Manchester)
Manchester, M20 3LJ,
Salford Royal NHS Foundation Trust
Manchester

Other trials in United Kingdom

About this study

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.

Conditions: Alzheimer Disease
Being tested: [C11] Leucine PET scan, [18F] Flutemetamol PET scan, MRI scan
Keywords: [11C]-Leucine, Positron Emission Tomography, Cerebral Protein Synthesis
Medical subject headings: Alzheimer Disease

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

[C11] Leucine PET scanDiagnostic test
Each participant will receive an i.v. bolus of the PET radioligand, [11C]-Leucine (<100 μg), for each scan. [11C]-Leucine is a PET radioligand has been used and studied clinically (17-23) at micro-doses (<100 μg) with no adverse effects.
[18F] Flutemetamol PET scanDiagnostic test
Each participant will receive an i.v. bolus of the PET radioligand, [18F]-Flutemetamol (< 10 μg), for each scan.
MRI scanDiagnostic test
Scans will be performed on a 1.5T Philips scanner including a 3D T1-weighted scan for co-registration with PET scans and rating of hippocampal atrophy, as well as standard T1 and T2-weighted sequences for rating of white matter lesions.

Study groups in NCT05491902
Study group	Role	What they receive
Early onset mild to moderate AD		Patients aged 50 to 69 Receives: Diagnostic Test: [C11] Leucine PET scan; Diagnostic Test: [18F] Flutemetamol PET scan; Diagnostic Test: MRI scan
Late onset mild to moderate AD		Patients aged 70 and above Receives: Diagnostic Test: [18F] Flutemetamol PET scan; Diagnostic Test: MRI scan
Older Healthy Volunteer		Aged 50 to 69 Receives: Diagnostic Test: [C11] Leucine PET scan; Diagnostic Test: [18F] Flutemetamol PET scan; Diagnostic Test: MRI scan
Younger Healthy Volunteer		Aged 18 - 25 Receives: Diagnostic Test: [C11] Leucine PET scan; Diagnostic Test: MRI scan

What is being measured

The primary outcome is the main question the study is designed to answer.

Regional changes in Protein Synthesis Rate in AD brain compared to age-matched controls
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.
Measured: 2 years after completion of patient recruitment
Regional changes in Protein Synthesis Rate in healthy controls
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.
Measured: 2 years after completion of patient recruitment

Secondary outcomes (1)

Regional changes in Protein Synthesis Rate in AD patients
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.
Measured: 2 years after completion of patient recruitment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

9 Oct 201715 Oct 2020

First posted8 Aug 2022
Study start9 Oct 2017
Primary completion15 Oct 2020
Study completion15 Oct 2020

Why it stopped: 11C-leucine no longer available at Wolfson Molecular Imaging Centre (after suspension of recruitment due to COVID pandemic)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
More trials run by University of ManchesterThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Cross-sectional
Enrolment: 10 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05491902
Sponsor's protocol ID: 16/NW/0705
Status last verified: Aug 2022
First submitted: 28 Sep 2021
Last updated: 8 Aug 2022
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Alzheimer Disease trials

Study at a glance

From the registry record, last updated by the sponsor on 8 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Pilot PET Study of Regional Cerebral Protein Synthesis in Alzheimer's
ClinicalTrials.gov ID: NCT05491902
Acronym / sponsor ID: 16/NW/0705
Conditions: Alzheimer Disease
Keywords: [11C]-Leucine, Positron Emission Tomography, Cerebral Protein Synthesis
Study type: Observational
Recruitment status: TerminatedReason stopped: 11C-leucine no longer available at Wolfson Molecular Imaging Centre (after suspension of recruitment due to COVID pandemic)
Enrolment: 10 participants (actual)
Lead sponsor: University of ManchesterUniversity, hospital or other
Collaborators: GlaxoSmithKline
Study start: 9 Oct 2017 (actual)
Primary completion: 15 Oct 2020 (actual)
Study completion: 15 Oct 2020 (actual)
First posted: 8 Aug 2022 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Study design

Observational model: Cohort
Time perspective: Cross-sectional
Number of arms: 4

Arm	Type	Receives
Early onset mild to moderate AD	–	Diagnostic Test: [C11] Leucine PET scan, Diagnostic Test: [18F] Flutemetamol PET scan, Diagnostic Test: MRI scanPatients aged 50 to 69
Late onset mild to moderate AD	–	Diagnostic Test: [18F] Flutemetamol PET scan, Diagnostic Test: MRI scanPatients aged 70 and above
Older Healthy Volunteer	–	Diagnostic Test: [C11] Leucine PET scan, Diagnostic Test: [18F] Flutemetamol PET scan, Diagnostic Test: MRI scanAged 50 to 69
Younger Healthy Volunteer	–	Diagnostic Test: [C11] Leucine PET scan, Diagnostic Test: MRI scanAged 18 - 25

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Accepted
Age groups: Adult, Older adult
Study population: Up to 12 AD participants will be recruited by the Salford Royal Foundation Trust in collaboration with clinical partners in appropriate clinical services for dementia. Up to 12 healthy controls will be recruited by approaching spouses and carers of patients or through the "Join Dementia Research" and "Citizen Scientist Salford" networks.

Key inclusion criteria (46 listed)

Are males or females between 50 and 69 years of age, inclusive, with onset of symptoms before age 65;
Meet the clinical criteria of the National Institute on Aging and the Alzheimer's Association workgroup for probable AD [25]. They have a significant cognitive impairment, Mini Mental State Examination (MMSE) score between 10 and 24 inclusive. Imaging biomarkers (hippocampal volume and cortical amyloid deposition) will be recorded for exploratory correlational analysis with PSR, but will not be used as criteria for inclusion;
Have a caregiver who can report on their mental status and activities of daily
living (ADL);
Must have capacity and be able to give informed consent.

Key exclusion criteria (13 listed)

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;

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
[C11] Leucine PET scanEach participant will receive an i.v. bolus of the PET radioligand, [11C]-Leucine (<100 μg), for each scan. [11C]-Leucine is a PET radioligand has been used and studied clinically (17-23) at micro-doses (<100 μg) with no adverse effects.	Diagnostic test	Early onset mild to moderate AD, Older Healthy Volunteer, Younger Healthy Volunteer
[18F] Flutemetamol PET scanEach participant will receive an i.v. bolus of the PET radioligand, [18F]-Flutemetamol (< 10 μg), for each scan.	Diagnostic test	Early onset mild to moderate AD, Late onset mild to moderate AD, Older Healthy Volunteer
MRI scanScans will be performed on a 1.5T Philips scanner including a 3D T1-weighted scan for co-registration with PET scans and rating of hippocampal atrophy, as well as standard T1 and T2-weighted sequences for rating of white matter lesions.	Diagnostic test	Early onset mild to moderate AD, Late onset mild to moderate AD, Older Healthy Volunteer, Younger Healthy Volunteer

Primary outcome

Regional changes in Protein Synthesis Rate in AD brain compared to age-matched controls
Time frame: 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
Time frame: 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.

1 secondary outcome

Regional changes in Protein Synthesis Rate in AD patients
Time frame: 2 years after completion of patient recruitment

Results and safety

The study was stopped early (reason given: 11C-leucine no longer available at Wolfson Molecular Imaging Centre (after suspension of recruitment due to COVID pandemic)). Results are not available in the source record.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Aug 2022.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

2 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Alzheimer Disease, run by University of Manchester at 2 sites in United Kingdom.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 46 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 8 Aug 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Regional changes in Protein Synthesis Rate in AD brain compared to age-matched controls (time frame: 2 years after completion of patient recruitment). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05491902.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Aug 2022.