Evaluation of Association Between Testosterone Levels, Dementia, and Adverse Mental Health Outcomes

Depression Clinical Trial

Official title:

Evaluation of a Causal Association Between Testosterone Levels, Dementia, and Adverse Mental Health Outcomes: A Mendelian Randomization Analysis

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04743466
• Other study ID #: 2019-1061
• Secondary ID: NCI-2020-1378220
• Status: Recruiting
• Start date: February 13, 2020
• Est. completion date: November 30, 2025

Study information

• Verified date: February 2024
• Source: M.D. Anderson Cancer Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This study evaluates the association between testosterone levels and risk of dementia and adverse mental health outcomes (e.g. depression and anxiety). It is not known whether low testosterone levels may be associated with an increased risk of dementia. Learning about the association between testosterone levels and risk of dementia may help determine the long-term effects of androgen deprivation therapy and may help improve quality of life.

Description:

PRIMARY OBJECTIVE: I. To use a Mendelian randomization study design to determine whether genetically predicted decreased testosterone levels are associated with an increased risk of dementia. SECONDARY OBJECTIVE: I. To examine whether genetically predicted decreased testosterone levels are associated with worse cognitive function and adverse mental health outcomes. OUTLINE: Patients' records from institutional or national biobanks are reviewed.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 700000
• Est. completion date: November 30, 2025
• Est. primary completion date: November 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Have volunteered to participate in institutional or national biobanks, mainly the UK Biobank and the Kaiser Permanente Research Bank, and those that have previously participated in studies that resulted in de-identified clinical and genetic data being make available on public archives, mainly the database of Genotypes and Phenotypes (dbGaP)
• No special populations (adults unable to consent, individuals not yet adults, pregnant women, or prisoners)

Related Conditions & MeSH terms

• Anxiety Disorder
• Anxiety Disorders
• Dementia
• Depression
• Genetic Diseases, Inborn
• Genetic Disorder
• Hematopoietic and Lymphoid Cell Neoplasm
• Malignant Solid Neoplasm
• Neoplasms

Intervention

Other:
• Electronic Health Record Review
Biobank records are reviewed

Locations

Country	Name	City	State
United States	M D Anderson Cancer Center	Houston	Texas

Sponsors (1)

Lead Sponsor	Collaborator
M.D. Anderson Cancer Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Association between germline genetic predictors (single nucleotide variants) of lower testosterone levels and dementia risk	Will utilize genetic variants associated with testosterone levels at genome-wide statistical significance thresholds (P < 5 x 10-8) in published meta-analyses. Will additionally conduct a genome-wide association study with testosterone values in the UK Biobank. Will construct a weighted genetic risk score based on the strength of each variant's association with testosterone levels in published datasets. The results of the weighted method will be scaled per standard deviation (SD) of testosterone levels so that effect sizes represent the odds ratio of the outcome (e.g. dementia) per genetically predicted SD decrease in testosterone levels. Will also utilize risk scores with less stringent significance thresholds in secondary analyses (P < 5 x 10-6).	Up to 2 years
Secondary	Depression	Association between low testosterone levels and depression will be examined. Will construct a weighted genetic risk score based on the strength of each variant's association with testosterone levels in published datasets. The results of the weighted method will be scaled per standard deviation (SD) of testosterone levels so that effect sizes represent the odds ratio of the outcome (e.g. dementia) per genetically predicted SD decrease in testosterone levels. Will also utilize risk scores with less stringent significance thresholds in secondary analyses (P < 5 x 10-6).	Up to 2 years
Secondary	Anxiety	Association between low testosterone levels and anxiety will be examined. Will construct a weighted genetic risk score based on the strength of each variant's association with testosterone levels in published datasets. The results of the weighted method will be scaled per standard deviation (SD) of testosterone levels so that effect sizes represent the odds ratio of the outcome (e.g. dementia) per genetically predicted SD decrease in testosterone levels. Will also utilize risk scores with less stringent significance thresholds in secondary analyses (P < 5 x 10-6).	Up to 2 years
Secondary	Cognitive/mental health	Association between low testosterone levels and cognitive/mental health will be examined. Will construct a weighted genetic risk score based on the strength of each variant's association with testosterone levels in published datasets. The results of the weighted method will be scaled per standard deviation (SD) of testosterone levels so that effect sizes represent the odds ratio of the outcome (e.g. dementia) per genetically predicted SD decrease in testosterone levels. Will also utilize risk scores with less stringent significance thresholds in secondary analyses (P < 5 x 10-6).	Up to 2 years