Mild Cognitive Impairment in Men Following Androgen Deprivation

This study is not yet open for participant recruitment.
Verified October 2012 by Imperial College London
Sponsor:
Information provided by (Responsible Party):
Imperial College London
ClinicalTrials.gov Identifier:
NCT01691976
First received: September 11, 2012
Last updated: October 16, 2012
Last verified: October 2012
  Purpose

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.


Condition Intervention
Prostate Cancer
Drug: Oestrogen Patches
Drug: LHRHa

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Open Label
Official Title: Mild Cognitive Impairment in Men Following Androgen Deprivation Therapy for Prostate Cancer: a Longitudinal fMRI and qEEG Pilot Study.

Resource links provided by NLM:


Further study details as provided by Imperial College London:

Primary Outcome Measures:
  • Objective evaluation of mild cognitive impairment on parietal fMRI signals [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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.


Secondary Outcome Measures:
  • Objective evaluation of mild cognitive impairment on non-parietal fMRI signals [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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.

  • Electroencephalographic evaluation of mild cognitive impairment [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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.

  • Subjective evaluation of mild cognitive impairment by CANTAB [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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.

  • Subjective evaluation of mild cognitive impairment by ADAS-cog [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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.


Other Outcome Measures:
  • Serum testosterone levels [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Measurement of change in serum testosterone levels at baseline and after six months of ADT with LHRHa.

  • Serum oestradiol levels [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Measurement of change in serum oestradiol levels at baseline and after six months of ADT with LHRHa.

  • Serum luteinising hormone levels [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Measurement of change in serum luteinising hormone levels at baseline and after six months of ADT with LHRHa.

  • Serum follicle-stimulating hormone levels [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Measurement of change in serum follicle stimulating hormone levels at baseline and after six months of ADT with LHRHa.

  • Serum albumin [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Measurement of change in serum albumin concentration at baseline and after six months of ADT with LHRHa.

  • Serum sex hormone binding globulin [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Measurement of change in serum sex hormone binding globulin concentration at baseline and after six months of ADT with LHRHa.


Estimated Enrollment: 10
Study Start Date: October 2012
Estimated Study Completion Date: March 2014
Estimated Primary Completion Date: September 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
No Intervention: Controls
Age-matched male patients with benign prostatic hyperplasia, otherwise healthy, as controls
Active Comparator: LHRHa
Prostate cancer patients receiving androgen deprivation therapy by luteinising hormone releasing-hormone agonists (LHRHa)
Drug: LHRHa
Luteinising hormone releasing-hormone agonists (LHRHa)
Experimental: Oestrogen
Prostate cancer patients recruited from the Prostate Adenocarcinoma TransCutaneous Hormones (PATCH) Trial, randomised to receive ADT via transdermal oestrogen patches.
Drug: Oestrogen Patches

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

Ages Eligible for Study:   50 Years to 90 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01691976

Contacts
Contact: Paul D Abel, ChM, FRCS 020 8383 2268 p.abel@imperial.ac.uk
Contact: Syed IA Shah, MBBS, MPhil 07466332905 s.shah10@imperial.ac.uk

Locations
United Kingdom
Imperial College Healthcare NHS Trust Not yet recruiting
London, United Kingdom, W12 0NN
Principal Investigator: Paul D Abel, ChM, FRCS         
Sponsors and Collaborators
Imperial College London
Investigators
Study Chair: Paul D Abel, ChM, FRCS Imperial College London and Imperial College Healthcare NHS Trust
Principal Investigator: Syed IA Shah, MBBS, MPhil Imperial College London and Imperial College Healthcare NHS Trust
Principal Investigator: Adam Waldman Imperial College Healthcare NHS Trust
Principal Investigator: Basant K Puri Imperial College Healthcare NHS Trust
Principal Investigator: Pat Price Imperial College London
  More Information

No publications provided

Responsible Party: Imperial College London
ClinicalTrials.gov Identifier: NCT01691976     History of Changes
Other Study ID Numbers: CRO2017
Study First Received: September 11, 2012
Last Updated: October 16, 2012
Health Authority: United Kingdom: Research Ethics Committee
United Kingdom: National Health Service

Keywords provided by Imperial College London:
Mild cognitive impairment
Androgen deprivation therapy

Additional relevant MeSH terms:
Prostatic Neoplasms
Cognition Disorders
Genital Neoplasms, Male
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Genital Diseases, Male
Prostatic Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Androgens
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on April 23, 2014