Prostate CancerNCT02061345
PET Imaging in MCI Following ADT for PCa
An observational study of Prostate Cancer and Mild Cognitive Impairment, run by Imperial College London at 1 site in United Kingdom.
Trial summary
Mild cognitive impairment (MCI) with ageing is thought in part to be related to reduced serum sex hormones which is well-recognized, especially in females, but poorly understood. International studies assessing hormone replacement therapy (HRT) to prevent/reduce MCI are ongoing. Read more about this study
- Who is it for?
- Ages 50 to 80 years, men only
- Conditions the study is for
- Prostate Cancer, Mild Cognitive Impairment
- How many people
- 11 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Apr 2014to Jan 2022
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 50 to 80 years
- Men only
- No healthy volunteers
- Adult, Older adult
Study population: A total of 12 prostate cancer patients on ADT with LHRHa will be recruited for the imaging part of the study; six patients having significant cognitive impairment attributable to LHRHa and six patients without cognitive impairment.
Who may be able to join
- Prostate cancer patients between the ages 50 to 80 years on ADT with LHRHa for for 3 months up to a year.
- Able to give written informed consent.
- Able to lie still for up to 90 minutes for a PET scan.
- Not claustrophobic and so able to undergo an MRI scan.
Who cannot join
- Patients with a known history of organic brain disorders and associated dementia, delirium and other specific neuropsychiatric conditions, including stroke and head injury.
- Patients who are clinically assessed as having MCI prior to starting ADT.
- Patients with a medical prognosis of less than 3 months.
- Patients who are claustrophobic.
- Patients who have any metal implanted in their body e.g. heart pacemaker, cochlear implant or any other electronic device.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Imperial College Healthcare NHS Trust
London, W6 8RF
About this study
Official title: A PET Imaging Study to Detect the Presence of Activated Microglia in the Brains of Prostate Cancer Patients Who Develop Mild Cognitive Impairment Following Androgen Deprivation Therapy
Mild cognitive impairment (MCI) with ageing is thought in part to be related to reduced serum sex hormones which is well-recognized, especially in females, but poorly understood. International studies assessing hormone replacement therapy (HRT) to prevent/reduce MCI are ongoing. MCI leads to morbidity, reduced quality of life and substantial healthcare costs. The commonest therapeutically induced reduction in sex hormone level in men is treatment of prostate cancer (PCa). PCa is androgen dependent and androgen deprivation therapy (ADT) suppressing testosterone to castrate levels is key therapy for advanced disease. About one million men worldwide have received ADT for PCa, mostly using luteinising hormone releasing hormone agonists (LHRHa) although oral oestrogens were used in the past; eventually perhaps 4% of Caucasians may be castrated. MCI as a side effect of castration in men remains poorly researched. This study aims to demonstrate that pathological changes occur in the brains of a significant proportion of prostate cancer patients subjected to ADT that correlate with MCI symptoms. Highlighting the pathological changes of MCI should improve understanding and interventions for slowing/preventing MCI in PCa survivors. Brain scans employing positron emission tomography (PET) imaging technique will be used to detect the presence of pathological changes in the brain that relate to ADT induced MCI. MCI will be assessed by neuropsychological assessments (standard paper-based questionnaires and online) and its neural basis will be investigated using magnetic resonance imaging (MRI).
Read the detailed description
In males, MCI with aging is thought in part to be related to reduction in serum androgen level and international studies are on-going to prevent age-related cognitive decline using androgen replacement therapy. Reduction in cognitive function often leads to morbidity and reduction in quality of life. The commonest therapeutically induced reduction in sex hormone level in men is in the treatment of prostate cancer. As prostate cancer is androgen dependent for growth, androgen-deprivation therapy (ADT) to suppress serum testosterone level to castration levels (< 1.7mM) is the key therapeutic intervention for advanced disease. Up to 1 million men worldwide are estimated to have been prescribed ADT for prostate cancer, mostly using luteinising hormone releasing hormone agonists (LHRHa). ADT is now also used to treat some early prostate cancer and as early asymptomatic prostate cancer is increasingly being diagnosed and treated following screening with serum prostate-specific antigen (PSA) measurement, estimates suggest that eventually up to 4% of all Caucasians will be castrated, some of them remaining on ADT for as long as 10 years or more. ADT is associated with considerable adverse effects, including MCI. Up to 69% of men showed MCI after six to nine months of ADT, with a decline in at least one cognitive area, most commonly visuospatial ability and executive function. Little work has been done to quantify MCI due to ADT, understand the mechanism, predict which patients will be affected and determine ways of reducing this side effect.
Establishing the presence of pathophysiology in ADT induced MCI first is important due to the lack of understanding of the underlying mechanism. A plausible scientific approach in this regard appears to be the use of the brain's immunological response to pathology using a PET imaging ligand for activated microglia. Brain microglia have been demonstrated to be highly responsive to brain injury and are rapidly activated in an attempt to envelope/ contain the focal pathology. When activated, brain microglia have been shown to express the translocator protein (TSPO). The 18 kilo-Dalton (KDa) translocator protein (TSPO) formerly known as the peripheral benzodiazepine receptor (PBR) is widely expressed in the body but is particularly enriched up to 20 to 50 fold in steroid synthesising tissues. High TSPO expression has also been reported in immune cells such as macrophages and monocytes and TSPO is a well-characterised marker of neuroinflammation. PET imaging ligands have been developed for TSPO and used successfully for researching a range of brain disorders. While such imaging does not provide mechanistic information of the underlying pathology, except for the exasperation of frank neuro-inflammation, it does offer a generic sensitive bio-marker for demonstrating the presence of an on-going active pathology
- Conditions
- Prostate Cancer, Mild Cognitive Impairment
- Keywords
- Prostate cancer, Androgen Deprivation Therapy, Mild Cognitive Impairment
- Medical subject headings
- Prostatic Neoplasms, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| MCI | Prostate cancer patients having mild cognitive impairment (MCI) attributable to ADT with LHRHa | |
| Control | Prostate cancer patients on ADT with LHRHa not having mild cognitive impairment |
What is being measured
The primary outcome is the main question the study is designed to answer.
PET Biomarker Uptake
The outcome measure is the increased uptake of 11-Carbon Peripheral Benzodiazepine Receptor-28 ([11C]PBR28) biomarker by activated microglia of patients demonstrating significant MCI with the primary endpoint of [11C]PBR28 uptake measured as a standardized uptake value (SUV)
Measured: Single time-point SUV in Hippocampus area on the day of the test
Secondary outcomes (1)
PET Biomarker Volume of Distribution
Secondary endpoint is the [11C]PBR28 total volume of distribution (VT)
Measured: Single time-point
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2014 (estimated)
- Study startApr 2014
- Primary completionDec 2016
- Study completionJan 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Prostate CancerStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe 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
- Case-control
- Time perspective
- Cross-sectional
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Paul D Abel, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02061345
- Sponsor's protocol ID
- 13HH0558
- Status last verified
- Nov 2023
- First submitted
- 11 Feb 2014
- Last updated
- 7 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Saleem A, Shah SIA, Mangar SA, Coello C, Wall MB, Rizzo G, Jones T, Price PM. Cognitive Dysfunction in Patients Treated with Androgen Deprivation Therapy: A Multimodality Functional Imaging Study to Evaluate Neuroinflammation. Prostate Cancer. 2023 Oct 18;2023:6641707. doi: 10.1155/2023/6641707. eCollection 2023.
PubMed 37885823
Study at a glance
From the registry record, last updated by the sponsor on 7 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PET Imaging Study to Detect the Presence of Activated Microglia in the Brains of Prostate Cancer Patients Who Develop Mild Cognitive Impairment Following Androgen Deprivation Therapy
- ClinicalTrials.gov ID
- NCT02061345
- Acronym / sponsor ID
- 13HH0558
- Conditions
- Prostate Cancer, Mild Cognitive Impairment
- Keywords
- Prostate cancer, Androgen Deprivation Therapy, Mild Cognitive Impairment
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- Apr 2014
- Primary completion
- Dec 2016 (actual)
- Study completion
- Jan 2022 (actual)
- First posted
- 12 Feb 2014 (estimated)
- Results
- Posted 7 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Mild cognitive impairment (MCI) with ageing is thought in part to be related to reduced serum sex hormones which is well-recognized, especially in females, but poorly understood. International studies assessing hormone replacement therapy (HRT) to prevent/reduce MCI are ongoing. MCI leads to morbidity, reduced quality of life and substantial healthcare costs. The commonest therapeutically induced reduction in sex hormone level in men is treatment of prostate cancer (PCa). PCa is androgen dependent and androgen deprivation therapy (ADT) suppressing testosterone to castrate levels is key therapy for advanced disease. About one million men worldwide have received ADT for PCa, mostly using luteinising hormone releasing hormone agonists (LHRHa) although oral oestrogens were used in the past; eventually perhaps 4% of Caucasians may be castrated. MCI as a side effect of castration in men remains poorly researched. This study aims to demonstrate that pathological changes occur in the brains of a significant proportion of prostate cancer patients subjected to ADT that correlate with MCI symptoms. Highlighting the pathological changes of MCI should improve understanding and interventions for slowing/preventing MCI in PCa survivors. Brain scans employing positron emission tomography (PET) imaging technique will be used to detect the presence of pathological changes in the brain that relate to ADT induced MCI. MCI will be assessed by neuropsychological assessments (standard paper-based questionnaires and online) and its neural basis will be investigated using magnetic resonance imaging (MRI).
Detailed description
In males, MCI with aging is thought in part to be related to reduction in serum androgen level and international studies are on-going to prevent age-related cognitive decline using androgen replacement therapy. Reduction in cognitive function often leads to morbidity and reduction in quality of life. The commonest therapeutically induced reduction in sex hormone level in men is in the treatment of prostate cancer. As prostate cancer is androgen dependent for growth, androgen-deprivation therapy (ADT) to suppress serum testosterone level to castration levels (< 1.7mM) is the key therapeutic intervention for advanced disease. Up to 1 million men worldwide are estimated to have been prescribed ADT for prostate cancer, mostly using luteinising hormone releasing hormone agonists (LHRHa). ADT is now also used to treat some early prostate cancer and as early asymptomatic prostate cancer is increasingly being diagnosed and treated following screening with serum prostate-specific antigen (PSA) measurement, estimates suggest that eventually up to 4% of all Caucasians will be castrated, some of them remaining on ADT for as long as 10 years or more. ADT is associated with considerable adverse effects, including MCI. Up to 69% of men showed MCI after six to nine months of ADT, with a decline in at least one cognitive area, most commonly visuospatial ability and executive function. Little work has been done to quantify MCI due to ADT, understand the mechanism, predict which patients will be affected and determine ways of reducing this side effect.
Establishing the presence of pathophysiology in ADT induced MCI first is important due to the lack of understanding of the underlying mechanism. A plausible scientific approach in this regard appears to be the use of the brain's immunological response to pathology using a PET imaging ligand for activated microglia. Brain microglia have been demonstrated to be highly responsive to brain injury and are rapidly activated in an attempt to envelope/ contain the focal pathology. When activated, brain microglia have been shown to express the translocator protein (TSPO). The 18 kilo-Dalton (KDa) translocator protein (TSPO) formerly known as the peripheral benzodiazepine receptor (PBR) is widely expressed in the body but is particularly enriched up to 20 to 50 fold in steroid synthesising tissues. High TSPO expression has also been reported in immune cells such as macrophages and monocytes and TSPO is a well-characterised marker of neuroinflammation. PET imaging ligands have been developed for TSPO and used successfully for researching a range of brain disorders. While such imaging does not provide mechanistic information of the underlying pathology, except for the exasperation of frank neuro-inflammation, it does offer a generic sensitive bio-marker for demonstrating the presence of an on-going active pathology
Study design
- Observational model
- Case-control
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MCI | – | –Prostate cancer patients having mild cognitive impairment (MCI) attributable to ADT with LHRHa |
| Control | – | –Prostate cancer patients on ADT with LHRHa not having mild cognitive impairment |
Who may qualify
- Ages
- 50 to 80 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- A total of 12 prostate cancer patients on ADT with LHRHa will be recruited for the imaging part of the study; six patients having significant cognitive impairment attributable to LHRHa and six patients without cognitive impairment.
Key inclusion criteria (4 listed)
- Prostate cancer patients between the ages 50 to 80 years on ADT with LHRHa for for 3 months up to a year.
- Able to give written informed consent.
- Able to lie still for up to 90 minutes for a PET scan.
- Not claustrophobic and so able to undergo an MRI scan.
Key exclusion criteria (5 listed)
- Patients with a known history of organic brain disorders and associated dementia, delirium and other specific neuropsychiatric conditions, including stroke and head injury.
- Patients who are clinically assessed as having MCI prior to starting ADT.
- Patients with a medical prognosis of less than 3 months.
- Patients who are claustrophobic.
- Patients who have any metal implanted in their body e.g. heart pacemaker, cochlear implant or any other electronic device.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
PET Biomarker Uptake
Time frame: Single time-point SUV in Hippocampus area on the day of the test
The outcome measure is the increased uptake of 11-Carbon Peripheral Benzodiazepine Receptor-28 ([11C]PBR28) biomarker by activated microglia of patients demonstrating significant MCI with the primary endpoint of [11C]PBR28 uptake measured as a standardized uptake value (SUV)
1 secondary outcome
PET Biomarker Volume of Distribution
Time frame: Single time-point
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 37885823Saleem A, Shah SIA, Mangar SA, Coello C, Wall MB, Rizzo G, Jones T, Price PM. Cognitive Dysfunction in Patients Treated with Androgen Deprivation Therapy: A Multimodality Functional Imaging Study to Evaluate Neuroinflammation. Prostate Cancer. 2023 Oct 18;2023:6641707. doi: 10.1155/2023/6641707. eCollection 2023.
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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.
Paul D Abel principal investigator
Imperial College London
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Prostate Cancer and Mild Cognitive Impairment, run by Imperial College London at 1 site 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 4 inclusion and 5 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: finished, as of the sponsor's last update on 7 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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?
Yes. Results are posted in the registry (first posted 7 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
PET Biomarker Uptake (time frame: Single time-point SUV in Hippocampus area on the day of the test). 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 NCT02061345, which also lists 1 linked publication.
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 7 Dec 2023.