Folate Study in Men With Advanced Prostate Cancer

November 9, 2025 updated by: Michael Liss, University of California, San Diego

A Phase II, Open Label, Randomized Controlled Pilot Study Evaluating Trimethoprim in Patients Commencing Androgen Deprivation Therapy for Prostate Cancer

The researchers hope to learn if Trimethoprim, 150mg taken daily for 3 months, is a safe and effective way to reduce folate levels at time of Androgen Deprivation Therapy (ADT) in men with advanced prostate cancer.

This study will help find out what effects, good and/or bad, this drug has on people who take it and on its effect on the disease. The safety of this drug in humans has been tested in prior research studies; however, some side effects may not yet be known.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

While taking part in this study, participants will be asked to attend approximately 4 to 7 visits - depending on what randomized arm they are in - with the researchers or study staff.

It may be necessary for participants to return to the hospital/clinic every 1-3 months as part of their regular care. Research procedures will be completed at the same time as these routine standard of care visits. Participants will be asked to stop taking any supplements or medications containing folic acid or potassium prior to enrolling in the study.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
50

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

INCLUSION CRITERIA

  1. Provision of signed and dated informed consent form.
  2. Stated willingness to comply with all study procedures and availability for the duration of the study.
  3. Age ≥ 18 years.
  4. Proven diagnosis of prostate cancer (intermediate unfavorable risk, high risk, very high risk localized per the 2025 NCCN guidelines), or metastatic hormone-sensitive prostate cancer with confirmation by pathology report and most recent prostate biopsy procedure note.
  5. Prostate cancer treatment naïve.
  6. Commencing androgen deprivation therapy for prostate cancer within 4 weeks of enrollment in the study. Note that radiotherapy and androgen receptor pathway inhibitors, apart from abiraterone, are allowed in both arms.
  7. Hemoglobin ≥ 11 g/dL.
  8. Red blood cell folate > 750 nmol/L.
  9. Homocysteine < 15 micromol/L.
  10. Creatine clearance within the normal range.
  11. Eastern Cooperative Oncology Group performance status 0-1
  12. Stated willingness to abstain from consumption of any supplements or medications containing folic acid or potassium.
  13. Ability to take oral medications and be willing to adhere to trimethoprim and androgen deprivation therapy regimens.
  14. For participants able to cause a pregnancy: use of condoms or other methods to ensure effective contraception with partner.
  15. Agreement to adhere to lifestyle considerations described in the protocol throughout study duration.

EXCLUSION CRITERIA

  1. Current use of memantine, phenytoin, and any medications that may significantly interact with TMP, including prohibited concomitant medications listed in the protocol.
  2. Current use of medications that would interfere with folate metabolism (for example, methotrexate).
  3. Treatment with another investigational drug while on this study.
  4. Treatment with hormone therapy, immunotherapy, chemotherapy and/or radiation therapy for any malignancies within the past 2 years. Patients with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible for this trial.
  5. History of renal or hepatic disease, including history of hepatitis B and C.
  6. Recurrent urinary tract infections, urinary retention, or neurological conditions affecting bladder function.
  7. Known hypersensitivity or allergy to trimethoprim.
  8. Hematological disorders (including megaloblastic anemia).
  9. Commencing chemotherapy for metastatic prostate cancer.

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

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Trimethoprim plus androgen deprivation therapy
Administration of trimethoprim to reduce folic acid levels at the time of standard of care androgen deprivation therapy.
Drug: Trimethoprim Tablets
Trimethoprim 150mg is administered once daily for 3 months
No Intervention: Standard of Care treatment
Standard of care treatment participants will have no intervention, only their prescribed androgen deprivation therapy.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Safety of Trimethoprim
Time Frame: From first dose of study therapy through 1 month after completion of study therapy.
Proportion of participants with adverse events and serious adverse events as graded by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE).
From first dose of study therapy through 1 month after completion of study therapy.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Serum Folate Levels
Time Frame: Baseline, 1, 2, 3 and 6 months
Comparing the TMP + SOC arm to the SOC alone arm will allow us to determine effect of TMP on measures of folic acid
Baseline, 1, 2, 3 and 6 months
Levels of Red Blood Cells (RBC) Folate
Time Frame: Baseline, 1, 2, 3 and 6 months
Comparing the TMP + SOC arm to the SOC alone arm will allow us to determine effect of TMP on measures of folic acid
Baseline, 1, 2, 3 and 6 months
Prostate Specific antigen (PSA) levels in blood
Time Frame: Baseline, 1, 2, 3 and 6 months
Prostate specific antigen (PSA) is an extensively studied biomarker with prognostic implications after initiation of ADT. In patients with prostate cancer, higher PSA after initiation of ADT is associated with shorter progression free survival
Baseline, 1, 2, 3 and 6 months
Urine exsomal PSMA
Time Frame: 1 month, 3 months and 6 months
A further emerging biomarker of prostate cancer is urine-derived exosome PSMA60. PSMA has been shown to be elevated in hormone resistant forms of metastatic prostate cancer60. The role of urine-derived exosome PSMA in metastatic disease and its relationship to folic acid and androgen deprivation is evolving and will be examined in this study.
1 month, 3 months and 6 months
Testosterone levels
Time Frame: 12, 18 and 24 months
Testosterone level is measured to determine progression free survival as part of standard of care
12, 18 and 24 months
Microbiome/metabolomic analysis
Time Frame: 1 month, 3 months and 6 months
Measure changes in gut microbiome after administration of TMP in men on ADT. Analysis of the gut microbiome in this context as a secondary aim will provide much needed data to help further understand the relationship of the gut microbiome in folic acid synthesis.
1 month, 3 months and 6 months

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of California, San Diego

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Michael A Liss, MD, PhD, University of California, San Diego

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 (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
July 30, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 30, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 2, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 12, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 9, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 812072

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Any manuscript, abstract or other publication or presentation of results or information arising in connection with the trial (including an ancillary trial involving trial subjects) will be prepared in conjuction with the study Data Safety Monitoring Board, and the statistician.

IPD Sharing Time Frame

At the time of publication in a peer review journal or presentation at a medical conference.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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