The Effect of Androgen Deprivation Therapy on Gut and Urinary Microbiota in Patients With Prostate Cancer

December 14, 2021 updated by: Chi Fai NG, Chinese University of Hong Kong

A Cross Sectional Study to Assess the Effect of Androgen Deprivation Therapy on Gut and Urinary Microbiota in Patients With Prostate Cancer

The incidence of prostate cancer is increasing in Hong Kong, as well as that of recurrent or metastatic prostate cancer. Androgen deprivation therapy (ADT) is the standard treatment for recurrent or metastatic prostate cancer, with side effects such as obesity, type 2 diabetes mellitus, metabolic syndrome, osteoporosis and cognitive impairment. With the improvement of treatment, the 5-year survival rate of recurrent and metastatic prostate cancer is up to 20%, and therefore increases the chances of developing such side effects.

Due to the introduction of next generation sequencing, investigators have more knowledge of the microbiota in our body, particularly the gut microbiota. Different studies have related gut dysbiosis with obesity, type 2 diabetes mellitus and metabolic syndrome. If investigators can show that ADT is leading to gut dysbiosis, this could be a way in preventing or treating the side effects of ADT.

This study aims to identify whether ADT in patients with prostate cancer will have different composition in their gut and urine microbiota.

Study Overview

Status

Completed

Conditions

Detailed Description

The prostate gland is a clinically important male accessory sex gland and vital for its production of semen. Prostate cancer (PCa) is now ranked 3th in annual incidence of male cancer and ranked 5th for cancer-related death in men in Hong Kong which accounts for about 10.9 deaths per 100,000 persons. (Hong Kong Cancer registry 2015) Its incidence is rising rapidly, almost tripled in the past 10 years. As the elderly population continues to increase, the impact of PCa on the men's health and also the burden on health care system will continue to rise.

Despite the improvement in awareness of the disease and also increasing use of serum prostate specific antigen, many patients still presented at a late stage that beyond cure by local therapy. Together with those patients suffered recurrent disease after local therapy,1 many PCa patients required the use of androgen deprivation therapy (ADT) for the control of disease.

However, unlike other malignancy, PCa is characterized by its slow progression nature and even for metastatic disease the 5-year survival is upto 20%. Therefore, while ADT can provide effective control of disease, there are increasing evidences suggesting that it can also result in many adverse effects in the patients, and these effects are particular important due to the long survival of these patients. From the western literature, the adverse effects can be quite diverse.2 Classical side effects after ADT include mood changes, hot flushes, change in cognitive function,3 loss of libido, erectile dysfunction, osteoporosis and pathological fracture.4 Also there are more and more evidences showed ADT will also altered the metabolic and cardiovascular status of the patients and resulted in increase in insulin resistance and increase in risk of cardiovascular related mortality.5-7 Similarly, from our local data, investigators also observed similar increase in adverse events also happened in Chinese patients treated with ADT.8

There are many possible mechanisms proposed for the occurrence of these adverse events in patients receiving ADT, including increase in obesity, dyslipidaemia, insulin resistance etc. All these factors will lead to increase in metabolic and cardiovascular risk. However, the exact link between of hypogonadism and the development of obesity, dyslipidaemia and insulin resistance was still unclear.

Since the development of the next-generation sequencing, the knowledge of the microbiota in different sites made much progress. Of all other sites, the gut was the most frequently studied. It was found that a number of different conditions were associated with the composition of the gut microbiota, like age9, environmental factors (e.g. diet10-12), medications and diseases like obesity13, inflammatory bowel disease14 and colorectal cancer.15 Other than those mentioned, gender difference in gut microbiota was found in animal studies16 as well as human studies.17-20

On the other hand, urinary microbiota was also found to have gender differences21. The mechanism of this difference is proposed by animal studies to be related to sex hormone16,22, and it was proposed to be due to the hormone-microbe interaction, or due to the sex-specific immune response.23

Recent studies has suggested castration will affect the guts microflora and resulted in the development of obesity in mice.22 However, whether similar effect in human was unknown. Moreover, if the microflora in men was also changed by ADT, this might be one of the underlying mechanism for the increase in cardiovascular and metabolic risk observed in men receiving ADT. Therefore, investigators would like to perform a prospective study to examine the relationship between ADT and gut and urinary microbiota, and also the possible relationship with the development of metabolic and cardiovascular complications in our local population.

Study Type

Observational

Enrollment (Actual)

214

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Hong Kong
      • Sha Tin, Hong Kong
        • Prince Of Wales Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Sampling Method

Non-Probability Sample

Study Population

300 Patients (150 patients with ADT usage and 150 patients with radical prostatectomy done) who fulfilled the above inclusion criteria with no exclusion criteria will be recruited for the study.

Description

Inclusion Criteria:

  • Adult patients with age greater than or equal to 18 years old, who are able to provide consent
  • Patients who was diagnosed to have prostate cancer
  • Patients either received continue ADT treatment for at least more than 6 months or have radical prostatectomy performed more than 6 months ago.

Exclusion Criteria:

  • Recent use of antibiotics within one month
  • History of urinary tract infection in preceding year

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
ADT Group
Participants received continue ADT treatment for at least more than 6 months
RRP Group
Participants have radical prostatectomy performed more than 6 months ago.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Difference in the composition of gut microbiome in prostate cancer patients with or without ADT
Time Frame: Baseline (one-time point only)
Total bacterial DNA was extracted from fecal / urine samples by using the bead-beating method with Qiagen QIAamp DNA Microbiome kit. Extracted DNA will be quantified by Nanodrop for PCR reaction.
Baseline (one-time point only)
Difference in the composition of urinary microbiome in prostate cancer patients with or without ADT
Time Frame: Baseline (one-time point only)
Total bacterial DNA was extracted from fecal / urine samples by using the bead-beating method with Qiagen QIAamp DNA Microbiome kit. Extracted DNA will be quantified by Nanodrop for PCR reaction.
Baseline (one-time point only)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Chinese University of Hong Kong

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 12, 2018

Primary Completion (Actual)

June 7, 2021

Study Completion (Actual)

June 7, 2021

Study Registration Dates

First Submitted

March 21, 2019

First Submitted That Met QC Criteria

March 21, 2019

First Posted (Actual)

March 25, 2019

Study Record Updates

Last Update Posted (Actual)

December 16, 2021

Last Update Submitted That Met QC Criteria

December 14, 2021

Last Verified

December 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CRE 2018.280

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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