Testosterone, Cognition, Ageing, and Cancer

Cancer-related Cognitive Impairment Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03452436
• Other study ID #: TCAC
• Status: Completed
• Start date: February 12, 2018
• Est. completion date: March 1, 2020

Study information

• Verified date: April 2019
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 133
• Est. completion date: March 1, 2020
• Est. primary completion date: March 1, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cancer-related Cognitive Impairment
• Cognitive Dysfunction

Locations

Country	Name	City	State
Denmark	Aarhus University Hospital	Aarhus

Sponsors (2)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Global cognitive functioning	Changes in global cognitive composite score as measured with neuropsychological tests specified under "Secondary Outcome Measures".	Baseline and 6 months' follow-up
Secondary	Visuospatial ability	Changes in visuospatial ability as measured with WAIS-IV Matrix Reasoning.	Baseline and 6 months' follow-up
Secondary	Visuospatial ability	Changes in visuospatial ability as measured with WAIS-IV Figure Weights.	Baseline and 6 months' follow-up
Secondary	Visuospatial ability	Changes in visuospatial ability as measured with WAIS-IV Visual Puzzles.	Baseline and 6 months' follow-up
Secondary	Visuospatial ability	Changes in visuospatial ability as measured with WAIS-IV Block Design.	Baseline and 6 months' follow-up
Secondary	Processing speed	Changes in processing speed as measured with Trail Making Test A.	Baseline and 6 months' follow-up
Secondary	Processing speed	Changes in processing speed as measured with WAIS-IV Coding.	Baseline and 6 months' follow-up
Secondary	Attention	Changes in attention as measured with WAIS-IV Digit Span Forwards.	Baseline and 6 months' follow-up
Secondary	Executive functioning	Changes in executive functioning as measured with Trail Making Test B.	Baseline and 6 months' follow-up
Secondary	Executive functioning	Changes in executive functioning as measured with Wisconsin Card Sorting Test.	Baseline and 6 months' follow-up
Secondary	Working memory	Changes in working memory as measured with WAIS-IV Digit Span Sequencing.	Baseline and 6 months' follow-up
Secondary	Working memory	Changes in working memory as measured with WAIS-IV Digit Span Backwards.	Baseline and 6 months' follow-up
Secondary	Verbal fluency	Changes in verbal fluency as measured with Controlled Oral Word Association Test.	Baseline and 6 months' follow-up
Secondary	Verbal learning and memory	Changes in verbal learning and memory as measured with Hopkins Verbal Learning Test-Revised.	Baseline and 6 months' follow-up
Secondary	Visuospatial learning and memory	Changes in visuospatial learning and memory as measured with WMS-III Visual Memory.	Baseline and 6 months' follow-up
Secondary	Testosterone levels	Changes in testosterone levels as measured with liquid chromatography tandem mass spectrometry (LC-MS/MS).	Baseline and 6 months' follow-up
Secondary	Brain grey matter	Changes in grey matter as measured with T1-weighted MRI.	Baseline and 6 months' follow-up
Secondary	Brain white matter	Changes in brain white matter as measured with diffusion-weighted MRI.	Baseline and 6 months' follow-up
Secondary	Moderator: APOE genotype	Genotype of the APOE gene obtained by TaqMan-genotyping the appropriate single nucleotide polymorphisms.	Baseline
Secondary	Moderator: COMT genotype	Genotype of the COMT gene obtained by TaqMan-genotyping the appropriate single nucleotide polymorphism.	Baseline
Secondary	Moderator: BDNF genotype	Genotype of the BDNF gene obtained by TaqMan-genotyping the appropriate single nucleotide polymorphism.	Baseline
Secondary	Moderator: CAG repeat length of the AR gene	CAG repeat lenght of the AR gene obtained by TaqMan-genotyping the appropriate single nucleotide polymorphism.	Baseline
Secondary	Neurobehavioral symptoms (i.e., apathy, executive dysfunction, and disinhibition)	Changes in neurobehavioral symptoms as measured with The Frontal Systems Behavior Scale (FrsBe).	Baseline and 6 months' follow-up
Secondary	Perceived cognitive functioning	Changes in perceived cognitive functioning as measured with The Patient Assessment of Own Functioning Inventory (POAFI).	Baseline and 6 months' follow-up
Secondary	Health-related quality of life	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).	Baseline and 6 months' follow-up
Secondary	Health-related quality of life - Prostate Cancer	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).	Baseline and 6 months' follow-up
Secondary	Health-related quality of life - Testicular Cancer	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).	Baseline and 6 months' follow-up