Mild Cognitive Impairment in Men Following Androgen Deprivation

Prostate Cancer Clinical Trial

Official title:

Mild Cognitive Impairment in Men Following Androgen Deprivation Therapy for Prostate Cancer: a Longitudinal fMRI and qEEG Pilot Study.

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01691976
• Other study ID #: CRO2017
• Status: Withdrawn
• Phase: N/A
• Start date: October 2012
• Est. completion date: December 2013

Study information

• Verified date: November 2020
• Source: Imperial College London
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 50 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Prostate Cancer
• Prostatic Neoplasms

Intervention

Drug:
• Oestrogen Patches

• LHRHa
Luteinising hormone releasing-hormone agonists (LHRHa)

Locations

Country	Name	City	State
United Kingdom	Imperial College Healthcare NHS Trust	London

Sponsors (1)

Lead Sponsor	Collaborator
Imperial College London

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Serum testosterone levels	Measurement of change in serum testosterone levels at baseline and after six months of ADT with LHRHa.	6 months
Other	Serum oestradiol levels	Measurement of change in serum oestradiol levels at baseline and after six months of ADT with LHRHa.	6 months
Other	Serum luteinising hormone levels	Measurement of change in serum luteinising hormone levels at baseline and after six months of ADT with LHRHa.	6 months
Other	Serum follicle-stimulating hormone levels	Measurement of change in serum follicle stimulating hormone levels at baseline and after six months of ADT with LHRHa.	6 months
Other	Serum albumin	Measurement of change in serum albumin concentration at baseline and after six months of ADT with LHRHa.	6 months
Other	Serum sex hormone binding globulin	Measurement of change in serum sex hormone binding globulin concentration at baseline and after six months of ADT with LHRHa.	6 months
Primary	Objective evaluation of mild cognitive impairment on parietal fMRI signals	The primary outcome measure is the development of MCI following ADT with LHRHa, as evaluated by fMRI. The group change in the parietal blood oxygen level-dependent echoplanar imaging (BOLD EPI) fMRI signal associated with a three-dimensional rotation cognitive activation task at six-month follow-up compared with baseline.	6 months
Secondary	Objective evaluation of mild cognitive impairment on non-parietal fMRI signals	One of the secondary outcome measures is the development of MCI following ADT with LHRHa, as evaluated by the group change in non-parietal BOLD EPI fMRI signals associated with the three-dimensional rotation cognitive activation task at six-month follow-up compared with baseline.	6 months
Secondary	Electroencephalographic evaluation of mild cognitive impairment	One of the secondary outcome measures is the development of MCI following ADT with LHRHa, as evaluated by the electroencephalographic frequency changes associated with the three-dimensional rotation cognitive activation task at six-month follow-up compared with baseline.	6 months
Secondary	Subjective evaluation of mild cognitive impairment by CANTAB	One of the secondary outcome measures is the development of MCI following ADT with LHRHa, as evaluated by CANTAB changes associated with the three-dimensional rotation cognitive activation task at six-month follow-up compared with baseline.	6 months
Secondary	Subjective evaluation of mild cognitive impairment by ADAS-cog	One of the secondary outcome measures is the development of MCI following ADT with LHRHa, as evaluated by ADAS-cog changes associated with the three-dimensional rotation cognitive activation task at six-month follow-up compared with baseline.	6 months