Prostate CancerNCT01691976
Mild Cognitive Impairment in Men Following Androgen Deprivation
A study testing Oestrogen Patches and LHRHa in people with Prostate Cancer, run by Imperial College London at 1 site in United Kingdom.
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. Read more about this study
- Who is it for?
- Ages 50 to 90 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Prostate Cancer
- What is being tested?
- Oestrogen Patches and LHRHa
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2012to Dec 2013
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 90 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Imperial College Healthcare NHS Trust
London, W12 0NN
About this study
Official title: Mild Cognitive Impairment in Men Following Androgen Deprivation Therapy for Prostate Cancer: a Longitudinal fMRI and qEEG Pilot Study.
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.
Read the 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.
- Conditions
- Prostate Cancer
- Being tested
- Oestrogen Patches, LHRHa
- Keywords
- Mild cognitive impairment, Androgen deprivation therapy
- 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.
Oestrogen PatchesDrug
LHRHaDrug
Luteinising hormone releasing-hormone agonists (LHRHa)
| Study group | Role | What they receive |
|---|---|---|
| Controls | No intervention | Age-matched male patients with benign prostatic hyperplasia, otherwise healthy, as controls |
| LHRHa | Active comparator | Prostate cancer patients receiving androgen deprivation therapy by luteinising hormone releasing-hormone agonists (LHRHa) Receives: Drug: LHRHa |
| Oestrogen | Experimental | Prostate cancer patients recruited from the Prostate Adenocarcinoma TransCutaneous Hormones (PATCH) Trial, randomised to receive ADT via transdermal oestrogen patches. Receives: Drug: Oestrogen Patches |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 6 months
Secondary outcomes (4)
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.
Measured: 6 months
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.
Measured: 6 months
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.
Measured: 6 months
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.
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Sep 2012 (estimated)
- Study startOct 2012
- Primary completionDec 2013
- Study completionDec 2013
Why it stopped: No one recruited due to resource limitations. Issues with how complicated the study could be for patients so the study was later modified and turned into a different study.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Paul D Abel, ChM, FRCS, Study chair, Imperial College London and Imperial College Healthcare NHS TrustSyed IA Shah, MBBS, MPhil, Principal investigator, Imperial College London and Imperial College Healthcare NHS TrustAdam Waldman, Principal investigator, Imperial College Healthcare NHS TrustBasant K Puri, Principal investigator, Imperial College Healthcare NHS TrustPat Price, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01691976
- Sponsor's protocol ID
- CRO2017
- Status last verified
- Nov 2020
- First submitted
- 11 Sep 2012
- Last updated
- 20 Nov 2020
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mild Cognitive Impairment in Men Following Androgen Deprivation Therapy for Prostate Cancer: a Longitudinal fMRI and qEEG Pilot Study.
- ClinicalTrials.gov ID
- NCT01691976
- Acronym / sponsor ID
- CRO2017
- Conditions
- Prostate Cancer
- Keywords
- Mild cognitive impairment, Androgen deprivation therapy
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: No one recruited due to resource limitations. Issues with how complicated the study could be for patients so the study was later modified and turned into a different study.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Study start
- Oct 2012 (actual)
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 25 Sep 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Controls | No intervention | –Age-matched male patients with benign prostatic hyperplasia, otherwise healthy, as controls |
| LHRHa | Active comparator | Drug: LHRHaProstate cancer patients receiving androgen deprivation therapy by luteinising hormone releasing-hormone agonists (LHRHa) |
| Oestrogen | Experimental | Drug: Oestrogen PatchesProstate cancer patients recruited from the Prostate Adenocarcinoma TransCutaneous Hormones (PATCH) Trial, randomised to receive ADT via transdermal oestrogen patches. |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Oestrogen Patches | Drug | Oestrogen |
| LHRHaLuteinising hormone releasing-hormone agonists (LHRHa) | Drug | LHRHa |
Primary outcome
Objective evaluation of mild cognitive impairment on parietal fMRI signals
Time frame: 6 months
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.
4 secondary outcomes
Objective evaluation of mild cognitive impairment on non-parietal fMRI signals
Time frame: 6 months
Electroencephalographic evaluation of mild cognitive impairment
Time frame: 6 months
Subjective evaluation of mild cognitive impairment by CANTAB
Time frame: 6 months
Subjective evaluation of mild cognitive impairment by ADAS-cog
Time frame: 6 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2020.
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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, ChM, FRCS study chair
Imperial College London and Imperial College Healthcare NHS Trust
Syed IA Shah, MBBS, MPhil principal investigator
Imperial College London and Imperial College Healthcare NHS Trust
Adam Waldman principal investigator
Imperial College Healthcare NHS Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Oestrogen Patches and LHRHa in people with Prostate Cancer, 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 1 inclusion and 1 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: withdrawn, as of the sponsor's last update on 20 Nov 2020. 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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Objective evaluation of mild cognitive impairment on parietal fMRI signals (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 20 Nov 2020.