Testosterone, Cognition, Ageing, and Cancer

• ClinicalTrials.gov Identifier: NCT03452436
• Recruitment Status: Completed
• First Posted: March 2, 2018
• Last Update Posted: March 25, 2020
• Sponsor: University of Aarhus
• Collaborator: Aarhus University Hospital
• Information provided by (Responsible Party): University of Aarhus

Study Description

Brief Summary:

The primary aim of the study is - in a prospective controlled design - to examine whether treatment-induced decreases in testosterone acts as a mechanism of cancer-related cognitive impairment (CRCI) in testicular and prostate cancer patients.

Secondary aims are 1) to explore whether decreases in testosterone interacts with increasing age to cause more severe CRCI in older patients, 2) to explore underlying neurophysiological (brain morphology) mechanisms of CRCI, and 3) to evaluate selected genetic variants as possible moderators of CRCI.

Condition or disease
Cancer-related Cognitive Impairment

Detailed Description:

The study will include three groups with a total of 120 participants: A) Forty testicular cancer patients will be included and examined 1) shortly after orchiectomy and prior to any further treatment and 2) at 6 months' follow- up. B) Forty prostate cancer patients will be included and examined at two time-points: 1) prior to initiation of medical castration and radiotherapy and 2) at 6 months' follow- up. C) Forty age- and education-matched healthy controls will be included and assessed at a similar time-interval, i.e., at an initial examination and at a 6 month follow-up. Measures include a battery of neuropsychological/ cognitive tests, questionnaires, blood samples, and Magnetic Resonance Imaging (MRI).

Primary hypothesis

1. Treatment-induced decreases in testosterone will be associated with decline in global cognitive functioning from baseline to 6 months' follow- up in both testicular and prostate cancer patients.

   Secondary hypotheses

2. Treatment-induced decreases in testosterone will be associated with decline in individual cognitive domains (i.e., processing speed, attention, verbal fluency, executive functioning, working memory, verbal learning and memory, visuospatial learning and memory, and visuospatial ability) from baseline to 6 months' follow- up in both testicular and prostate cancer patients.
3. Decline in cognitive functioning from baseline to 6 months' follow- up in both testicular and prostate cancer patients will correspond to changes in grey matter as measured by T1-weighted MRI.
4. Decline in cognitive functioning from baseline to 6 months' follow- up in both testicular and prostate cancer patients will correspond to changes in brain white matter as measured with diffusion-weighted MRI.
5. Treatment-induced decreases in testosterone will be more strongly associated with decline in cognitive functioning in prostate cancer patients compared with testicular cancer patients due to more advanced age in the former group.
6. Treatment-induced decreases in testosterone will be more strongly associated with decline in cognitive functioning in both testicular and prostate cancer patients carrying the the Apolipoprotein E (APOE) ε4 allele, the Val catechol-O-methyltranferase (COMT) allele, the Val/Val Brain- derived neurotrophic factor (BDNF) genotype, and a short polymorphic CAG repeat length of the Androgen Receptor (AR) gene.
7. Treatment-induced decreases in testosterone will be associated with increases in neurobehavioral symptoms (i.e., apathy, executive dysfunction, and disinhibition) from baseline to 6 months' follow- up in both testicular and prostate cancer patients.
8. Treatment-induced decreases in testosterone will be associated with decreases in health-related quality of life from baseline to 6 months' follow- up in both testicular and prostate cancer patients.
9. Treatment-induced decreases in testosterone will be associated with decreases in perceived cognitive functioning from baseline to 6 months' follow- up in both testicular and prostate cancer patients.

Study Design

• Study Type: Observational
• Actual Enrollment: 133 participants
• Observational Model: Case-Control
• Time Perspective: Prospective
• Official Title: Testosterone, Cognition, Ageing, and Cancer - A Controlled, Prospective Study About the Association Between Testosterone and the Prevalence and Severity of Cancer Related Cognitive Impairment in Testicular and Prostate Cancer Patients.
• Actual Study Start Date: February 12, 2018
• Actual Primary Completion Date: March 1, 2020
• Actual Study Completion Date: March 1, 2020

Groups and Cohorts

Group/Cohort
Testicular cancer patients; Forty testicular cancer patients included after orchiectomy but prior to any further treatment.
Prostate cancer patients; Forty prostate cancer patients included prior to medical castration and radiotherapy.
Healthy controls; Forty age- and education-matched healthy controls (20 matched to testicular cancer patients, 20 matched to prostate cancer patients).

Outcome Measures

Primary Outcome Measures :

1. Global cognitive functioning [ Time Frame: Baseline and 6 months' follow-up ]
   Changes in global cognitive composite score as measured with neuropsychological tests specified under "Secondary Outcome Measures".

Secondary Outcome Measures :

1. Visuospatial ability [ Time Frame: Baseline and 6 months' follow-up ]
   Changes in visuospatial ability as measured with WAIS-IV Matrix Reasoning.
2. Visuospatial ability [ Time Frame: Baseline and 6 months' follow-up ]
   Changes in visuospatial ability as measured with WAIS-IV Figure Weights.
3. Visuospatial ability [ Time Frame: Baseline and 6 months' follow-up ]
   Changes in visuospatial ability as measured with WAIS-IV Visual Puzzles.
4. Visuospatial ability [ Time Frame: Baseline and 6 months' follow-up ]
   Changes in visuospatial ability as measured with WAIS-IV Block Design.
5. Processing speed [ Time Frame: Baseline and 6 months' follow-up ]
   Changes in processing speed as measured with Trail Making Test A.
6. Processing speed [ Time Frame: Baseline and 6 months' follow-up ]
   Changes in processing speed as measured with WAIS-IV Coding.
7. Attention [ Time Frame: Baseline and 6 months' follow-up ]
   Changes in attention as measured with WAIS-IV Digit Span Forwards.
8. Executive functioning [ Time Frame: Baseline and 6 months' follow-up ]
   Changes in executive functioning as measured with Trail Making Test B.
9. Executive functioning [ Time Frame: Baseline and 6 months' follow-up ]
   Changes in executive functioning as measured with Wisconsin Card Sorting Test.
10. Working memory [ Time Frame: Baseline and 6 months' follow-up ]
    Changes in working memory as measured with WAIS-IV Digit Span Sequencing.
11. Working memory [ Time Frame: Baseline and 6 months' follow-up ]
    Changes in working memory as measured with WAIS-IV Digit Span Backwards.
12. Verbal fluency [ Time Frame: Baseline and 6 months' follow-up ]
    Changes in verbal fluency as measured with Controlled Oral Word Association Test.
13. Verbal learning and memory [ Time Frame: Baseline and 6 months' follow-up ]
    Changes in verbal learning and memory as measured with Hopkins Verbal Learning Test-Revised.
14. Visuospatial learning and memory [ Time Frame: Baseline and 6 months' follow-up ]
    Changes in visuospatial learning and memory as measured with WMS-III Visual Memory.
15. Testosterone levels [ Time Frame: Baseline and 6 months' follow-up ]
    Changes in testosterone levels as measured with liquid chromatography tandem mass spectrometry (LC-MS/MS).
16. Brain grey matter [ Time Frame: Baseline and 6 months' follow-up ]
    Changes in grey matter as measured with T1-weighted MRI.
17. Brain white matter [ Time Frame: Baseline and 6 months' follow-up ]
    Changes in brain white matter as measured with diffusion-weighted MRI.
18. Moderator: APOE genotype [ Time Frame: Baseline ]
    Genotype of the APOE gene obtained by TaqMan-genotyping the appropriate single nucleotide polymorphisms.
19. Moderator: COMT genotype [ Time Frame: Baseline ]
    Genotype of the COMT gene obtained by TaqMan-genotyping the appropriate single nucleotide polymorphism.
20. Moderator: BDNF genotype [ Time Frame: Baseline ]
    Genotype of the BDNF gene obtained by TaqMan-genotyping the appropriate single nucleotide polymorphism.
21. Moderator: CAG repeat length of the AR gene [ Time Frame: Baseline ]
    CAG repeat lenght of the AR gene obtained by TaqMan-genotyping the appropriate single nucleotide polymorphism.
22. Neurobehavioral symptoms (i.e., apathy, executive dysfunction, and disinhibition) [ Time Frame: Baseline and 6 months' follow-up ]
    Changes in neurobehavioral symptoms as measured with The Frontal Systems Behavior Scale (FrsBe).
23. Perceived cognitive functioning [ Time Frame: Baseline and 6 months' follow-up ]
    Changes in perceived cognitive functioning as measured with The Patient Assessment of Own Functioning Inventory (POAFI).
24. Health-related quality of life [ Time Frame: Baseline and 6 months' follow-up ]
    Changes in health-related quality of life as measured with The European Organization for Research and Treatment of Cancer, Quality of Life questionnaire for cancer patients (EORTC QLQ-C30).
25. Health-related quality of life - Prostate Cancer [ Time Frame: Baseline and 6 months' follow-up ]
    Changes in disease specific health-related quality of life as measured with The European Organization for Research and Treatment of Cancer, Quality of Life Prostate Cancer Module (EORTC QLQ-PR25).
26. Health-related quality of life - Testicular Cancer [ Time Frame: Baseline and 6 months' follow-up ]
    Changes in disease specific health-related quality of life as measured with The European Organization for Research and Treatment of Cancer, Quality of Life Testicular Cancer Module (EORTC QLQ-TC25).

Biospecimen Retention:   Samples With DNA

Blood samples

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

Men with testicular and prostate cancer seen at Aarhus University Hospital. Age- and education matched healthy controls recruited from the general population of Central Denmark Region.

Criteria

Inclusion Criteria:

• Confirmed diagnosis of testicular cancer
• Confirmed diagnosis of prostate cancer and prescription of medical castration and radiotherapy

Exclusion Criteria:

• Previous cancer disease
• Previous central nervous system disease
• Brain metastases
• Severe psychiatric disease (e.g., schizophrenia, major depressive disorder)
• Insufficient Danish proficiency for neuropsychological testing

Contacts and Locations

Locations

Denmark

Aarhus University Hospital

Aarhus, Denmark, 8200

Sponsors and Collaborators

University of Aarhus

Aarhus University Hospital

Investigators

• Principal Investigator: Cecilie D R Clausen, MSc; Unit for Psychooncology & Health Psychology, Department of Oncology, Aarhus University
• Study Director: Robert Zachariae, Professor, DMSc; Unit for Psychooncology & Health Psychology, Department of Oncology, Aarhus University

More Information

• Responsible Party: University of Aarhus
• ClinicalTrials.gov Identifier: NCT03452436
• Other Study ID Numbers: TCAC
• First Posted: March 2, 2018
• Last Update Posted: March 25, 2020
• Last Verified: April 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by University of Aarhus:

Cancer-related Cognitive Impairment; Cognitive Dysfunction; Cognition Disorders; Neurocognitive Disorder; Testosterone; Endocrinology; Testicular Cancer; Prostate Cancer

Additional relevant MeSH terms:

Cognitive Dysfunction; Cognition Disorders; Neurocognitive Disorders; Mental Disorders