PET Imaging in MCI Following ADT for PCa

NCT ID: NCT02061345

Last Updated: 2023-12-07

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 11 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2014-04-30
• Study Completion Date: 2022-01-31

Brief 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. 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

Conditions

Prostate Cancer; Mild Cognitive Impairment

Keywords

Prostate cancer; Androgen Deprivation Therapy; Mild Cognitive Impairment

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

MCI

Prostate cancer patients having mild cognitive impairment (MCI) attributable to ADT with LHRHa

No interventions assigned to this group

Control

Prostate cancer patients on ADT with LHRHa not having mild cognitive impairment

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

1. Prostate cancer patients between the ages 50 to 80 years on ADT with LHRHa for for 3 months up to a year.

2. Able to give written informed consent.

3. Able to lie still for up to 90 minutes for a PET scan.

4. Not claustrophobic and so able to undergo an MRI scan.

Exclusion Criteria

1. Patients with a known history of organic brain disorders and associated dementia, delirium and other specific neuropsychiatric conditions, including stroke and head injury.

2. Patients who are clinically assessed as having MCI prior to starting ADT.

3. Patients with a medical prognosis of less than 3 months.

4. Patients who are claustrophobic.

5. Patients who have any metal implanted in their body e.g. heart pacemaker, cochlear implant or any other electronic device.

• Minimum Eligible Age: 50 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: MALE
• Accepts Healthy Volunteers: No

Sponsors

Imperial College London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Paul D Abel

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Locations

Imperial College Healthcare NHS Trust

London, , United Kingdom

Countries

United Kingdom

References

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.

Reference Type: RESULT

PMID: 37885823 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Other Identifiers

13HH0558

Identifier Type: -

Identifier Source: org_study_id