Clinical trial NCT01691976: Mild Cognitive Impairment in Men Following Androgen Deprivation
Official title: Mild Cognitive Impairment in Men Following Androgen Deprivation Therapy for Prostate Cancer: a Longitudinal fMRI and qEEG Pilot Study.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: NA
Conditions: Prostate Cancer
Keywords: Mild cognitive impairment
Androgen deprivation therapy
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2012-09-25
Enrollment: 0
Sex: MALE
Minimum age (years): 50
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: MCI with ageing is thought in part to be related to reduced serum sex hormones which is well-recognised, 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 pilot study will quantify the extent of MCI in men receiving ADT with LHRHa and oestrogen to inform the design of a larger study to understand mechanisms, predict affected patients and determine ways of reducing MCI. Researching relationships of sex hormones and MCI should improve understanding and interventions for slowing/preventing MCI in PCa survivors. HRT in women slows MCI. Alternatives for ADT include parenteral oestrogen. The PATCH clinical trial comparing transdermal oestrogen with LHRHa offers an opportunity to assess oestrogen as preventative for male MCI. Functional magnetic resonance imaging (fMRI), quantitative electroencephalography (qEEG) and neuropsychological tests will be used to test this hypothesis.

Detailed description: Changes in cognitive function related to altered serum sex hormone levels are well-recognised but poorly understood. Mild cognitive impairment (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 MCI 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 PSA measurement, estimates suggest that eventually up to 4% of all Caucasians will be castrated.

MCI is a recognized side effect of ADT but little work has been done to quantify the effect, understand the mechanism, predict which patients will be affected and determine ways of reducing this side effect. Researching relationships of sex hormones and MCI should improve understanding and interventions for slowing/preventing MCI in PCa survivors. Hormone replacement therapy (HRT) in women slows the development of MCI. Alternatives for ADT include parenteral oestrogens. The PATCH clinical trial comparing transdermal oestrogen with LHRHa offers an opportunity to assess oestrogen as preventative for male MCI. Functional magnetic resonance imaging (fMRI), quantitative electroencephalography (qEEG) and neuropsychological tests will be used to test this hypothesis. Insight into the effect of changes in serum sex hormones on MCI may provide a guide to improving MCI in aging and improve the quality of life of prostate cancer survivors.

This study aims to (i) measure cognitive changes in prostate cancer patients receiving ADT with either LHRHa or transdermal oestrogen and (ii) relate MCI to changes in serum hormone levels. Simultaneous high-resolution fMRI of the brain and 64-channel qEEG will be used for the first time in this patient group. MCI will be investigated by assessing changes in parietal lobe activation to mental rotation tasks and changes in global resting-state fMRI and qEEG activity and comparisons will be made with the cognitive assessment carried out by neuropsychological tests.

Eligibility criteria: Inclusion Criteria:

* Male patients between the ages 50 to 90 years beginning ADT with LHRHa or PATCH participants randomised to either LHRHa or transdermal oestrogen for either newly diagnosed advanced prostate cancer or previously treated with radical radiotherapy or surgery and now having a rising prostate specific antigen will be included in the study.

Exclusion Criteria:

* Patients with a known history of dementia will be excluded as well as those patients who have received any prior hormone therapy for localised prostate cancer.

Primary outcomes:
measure: Objective evaluation of mild cognitive impairment on parietal fMRI signals
timeFrame: 6 months
Secondary outcomes:
measure: Objective evaluation of mild cognitive impairment on non-parietal fMRI signals
timeFrame: 6 months
measure: Electroencephalographic evaluation of mild cognitive impairment
timeFrame: 6 months
measure: Subjective evaluation of mild cognitive impairment by CANTAB
timeFrame: 6 months
measure: Subjective evaluation of mild cognitive impairment by ADAS-cog
timeFrame: 6 months
Other outcomes:
measure: Serum testosterone levels
timeFrame: 6 months
measure: Serum oestradiol levels
timeFrame: 6 months
measure: Serum luteinising hormone levels
timeFrame: 6 months
measure: Serum follicle-stimulating hormone levels
timeFrame: 6 months
measure: Serum albumin
timeFrame: 6 months
measure: Serum sex hormone binding globulin
timeFrame: 6 months
Locations:
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
affiliation: Imperial College London and Imperial College Healthcare NHS Trust
name: Paul D Abel, ChM, FRCS
role: STUDY_CHAIR
affiliation: Imperial College London and Imperial College Healthcare NHS Trust
name: Syed IA Shah, MBBS, MPhil
role: PRINCIPAL_INVESTIGATOR
affiliation: Imperial College Healthcare NHS Trust
name: Adam Waldman
role: PRINCIPAL_INVESTIGATOR
affiliation: Imperial College Healthcare NHS Trust
name: Basant K Puri
role: PRINCIPAL_INVESTIGATOR
affiliation: Imperial College London
name: Pat Price
role: PRINCIPAL_INVESTIGATOR
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