BPH (Benign Prostatic Hyperplasia)Phase 2NCT06944145
New Treatment Strategies and Epigenetic Biomarker for Management of Benign Prostatic Hyperplasia
A Phase 2 study testing raloxifene and Finasteride in people with BPH (Benign Prostatic Hyperplasia) and Lower Urinary Track Symptoms, run by Beth Israel Deaconess Medical Center at 1 site in United States.
Trial summary
SRD5A2 is a critical enzyme for prostatic development and growth, and the SRD5A2 inhibitor, finasteride, is used to treat benign prostatic hyperplasia (BPH). SRD5A2 is absent in 30% of normal adult men, which explains the resistance of a subset of patients to this commonly prescribed drug. Read more about this study
- Who is it for?
- Ages 18 years and older, men only
- Conditions the study is for
- BPH (Benign Prostatic Hyperplasia), Lower Urinary Track Symptoms
- What is being tested?
- raloxifene and Finasteride
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 242 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Dec 2025to 31 Aug 2030
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- ≥18 yrs old on the day of study consent;
- Finasteride has been recommended for treatment of BPH by a physician;
- PSA <20ng/ml within the last six months;
- Willingness to maintain any current genitourinary medications (e.g., beta agonists, alpha blockers, anticholinergics);
- Patient is able and willing to provide written informed consent.
Who cannot join
- Active or past history of venous thromboembolism, including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis;
- Previous diagnosis with any prostatic malignancy or precancerous lesions (atypical glandular foci);
- History of pelvic radiation;
- Actively receiving intravesical therapy for bladder cancer;
- Received treatment with any demethylating medications (azacitidine, decitabine, zebularine, guadecitabine, hydralazine);
- Current use of warfarin;
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- Prior treatment with 5ARI medications (e.g., Finasteride or Dutasteride) in the last year;
- Diagnosed with diabetes mellitus;
- Diagnosed with any neurodegenerative diseases;
- History of allergic reaction to any intravenous (IV) iron replacement products;
- Currently taking cholestyramine medication;
- Contraindications to MRI examination, which may include:
- Cardiac pacemaker
- Intracranial clips, metal implants, or external clips within 10mm of the head
- Previous metal injury in the eye or occupation risk to ferrous metal in the eye (e.g. metalworker)
- Claustrophobia that cannot be managed with benzodiazepine
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Yulia Mulugeta, 617-632-8890, ymuluget@bidmc.harvard.edu
About this study
Official title: A Phase 2b Randomized, Single-Center, Double Blind, Placebo Controlled, 2-Arm Study to Investigate Orally Administered Combination Therapies (5-alpha Reductase Inhibitor + Raloxifene) Compared With Monotherapy (5-alpha Reductase Inhibitor + Placebo) in Adult Patients With Benign Prostatic Hyperplasia (BPH)
SRD5A2 is a critical enzyme for prostatic development and growth, and the SRD5A2 inhibitor, finasteride, is used to treat benign prostatic hyperplasia (BPH). SRD5A2 is absent in 30% of normal adult men, which explains the resistance of a subset of patients to this commonly prescribed drug. This project proposes new combination therapies (5-ARI+raloxifene) and evaluates novel non-invasive biomarkers, based on alternative pathways that lead to prostatic enlargement.
Read the detailed description
Over 90% of adult males develop lower urinary tract symptoms (LUTS) secondary to bladder outlet obstruction by age 80 secondary to benign prostatic hyperplasia (BPH). BPH, the most common proliferative abnormality in humans, negatively impact the quality of life of 210 million men globally, accounting for significant life years lost. This study proposes to clinically evaluate the mechanisms of resistance to 5α-reductase inhibitor, finasteride, one of the more common drugs used to manage BPH and associated LUTS. Ongoing work has focused on steroid 5α-reductase 2 (SRD5A2, aka: 5α-reductase 2 [5AR2]), the enzyme responsible for prostatic development and growth. Investigations have revealed that expression of SRD5A2 is variable, and in fact, 30% of men do not express SRD5A2 in prostate tissues. Previous work, shows that somatic suppression of SRD5A2 during adulthood is dependent on epigenetic changes associated with methylation of the promoter region of the SRD5A2 gene. Studies indicate that (1) methylation of the SRDA2 is regulated by direct binding of the DNA-methyl transferase 1 (DNMT1) protein to the SRD5A2 promoter; (2) the inflammatory mediators TNF-α, NF-kB, and IL-6 regulate DNMT1 binding and subsequent methylation of the SRD5A2 promoter region; (3) clinical conditions associated with increased inflammation, age, and obesity, are associated with decreased expression of SRD5A via epigenetic modification; (4) in the absence of prostatic SRD5A2, alternate estrogenic pathways are upregulated, leading to an androgenic-to-estrogenic switch in the prostate gland, thus creating alternate pathways for prostatic growth. Therefore, it is hypothesized that (1) non- invasive assessment of SRD5A2 methylation status in peripheral blood can be an excellent indicator for resistance to 5ARI therapy, and (2) in men demonstrating hypermethylation of SRD5A2 and low protein expression (patients suspected of being resistant to 5ARI therapy), combination therapy (Selective Estrogen Receptor Modulators [SERMs]+5ARI) will serve as a better treatment strategy. To demonstrate the clinical significance of epigenetic changes to SRD5A2 and confirm its role in regulating sensitivity to 5ARI treatment, and to examine the role of estrogenic signaling blockade, a clinical trial is proposed with: Specific Aim 1: To assess the role of combination therapy (5ARI + SERM) in the treatment of BPH and to determine whether methylation of SRD5A2 promoter is a predictor for response to therapy. Specific Aim 2: To prospectively evaluate whether non-invasive radiologic prostate inflammatory markers can predict circulating WBCs SRD5A2 promoter methylation.
- Being tested
- raloxifene, Finasteride
- Keywords
- BPH, SRD5A2, Finasteride, LUTS
- Medical subject headings
- Prostatic Hyperplasia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
raloxifeneDrug
Participants in the Finasteride + Raloxifene Combination Therapy Arm will receive both Finasteride and Raloxifene as their intervention.
Participants randomized to the Finasteride + Raloxifene Combination Therapy arm will self-administer finasteride at 5 mg orally/day and raloxifene at 60 mg orally/day.
FinasterideDrug
Participants randomized to the Finasteride + Inactive Placebo Monotherapy arm will self-administer finasteride at 5 mg orally/day and placebo capsule daily.
| Study group | Role | What they receive |
|---|---|---|
| Finasteride + Inactive Placebo Monotherapy | Active comparator | Participants may be randomized into the Finasteride + Inactive Placebo Monotherapy arm. Receives: Drug: Finasteride |
| Finasteride + Raloxifene Combination Therapy | Experimental | Participants may be randomized into the Finasteride + Raloxifene Combination Therapy arm. Receives: Drug: raloxifene; Drug: Finasteride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical response to at 12 months after study enrollment
The primary endpoint is the clinical response (yes-no) to therapy at 12 months after study enrollment between the combination and monotherapy treatment groups. Clinical response will be defined as ≥3-point decrease in International Prostate Symptom Score between baseline and the 12-month timepoint, adjusting for baseline measure of International Prostate Symptom Score.
The minimal International Prostate Symptom Score is 0, denoting no symptoms, and the maximum score is 35, denoting severe symptoms.
Measured: From enrollment to the end of treatment at 12 months
Secondary outcomes (5)
Heterogeneity of clinical response to at 12 months after study enrollment by methylation score
Assessing the clinical response (yes-no) to therapy at 12 months after study enrollment between the combination and monotherapy treatment groups. Clinical response will be defined as ≥3-point decrease in International Prostate Symptom Score between baseline and the 12-month timepoint, adjusting for baseline measure of International Prostate Symptom Score. We will examine whether methylation score modifies the effect of treatment group on the primary endpoint by testing statistical interaction between treatment group and methylation score.
The minimal International Prostate Symptom Score is 0, denoting no symptoms, and the maximum score is 35, denoting severe symptoms.
Measured: From enrollment to the end of treatment at 12 months
Comparison of mean International Prostate Symptom Score between study arms
Mean 12-month International Prostate Symptom Score will be compared between study arms, adjusting for baseline International Prostate Symptom Score.
The minimal International Prostate Symptom Score is 0, denoting no symptoms, and the maximum score is 35, denoting severe symptoms.
Measured: From enrollment to the end of treatment at 12 months
Comparison of mean International Index of Erectile Function Questionnaire scores between study arms
Mean 12-month International Index of Erectile Function (IIEF) Questionnaire scores will be compared between study arms, adjusting for baseline International Index of Erectile Function score.
A score of 0 to 5 is awarded to each of the 15 questions that examine the 4 main domains of male sexual function: erectile function, orgasmic function, sexual desire and intercourse satisfaction. The overall minimum score is 0, which indicates poor erectile function and the maximum score is 75 indicating good erectile function.
Measured: From enrollment to the end of treatment at 12 months
Correlation between methylation and MRI scores
Measured: From enrollment to the end of treatment at 12 months
Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0
Comparison of treatment related adverse events by study arm.
Measured: From enrollment to the end of treatment at 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Apr 2025
- Study start3 Dec 2025
- Primary completion1 Jun 2029 (estimated)
- Study completion31 Aug 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for BPH (Benign Prostatic Hyperplasia)Studies of the same condition, open and under way.
- More trials run by Beth Israel Deaconess Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 242 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Beth Israel Deaconess Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Aria F. Olumi, MD, Beth Israel Deaconess Medical Center
- Investigators
- Aria Olumi, MD, Principal investigator, Beth Israel Deaconess Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06944145
- Sponsor's protocol ID
- 2025P000440
- Other IDs
- R01DK142211
- Status last verified
- Mar 2026
- First submitted
- 25 Mar 2025
- Last updated
- 23 Mar 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: All individual participant data collected throughout the trial. Data will be fully de-identified prior to sharing.
Study at a glance
From the registry record, last updated by the sponsor on 23 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 2b Randomized, Single-Center, Double Blind, Placebo Controlled, 2-Arm Study to Investigate Orally Administered Combination Therapies (5-alpha Reductase Inhibitor + Raloxifene) Compared With Monotherapy (5-alpha Reductase Inhibitor + Placebo) in Adult Patients With Benign Prostatic Hyperplasia (BPH)
- ClinicalTrials.gov ID
- NCT06944145
- Acronym / sponsor ID
- 2025P000440
- Keywords
- BPH, SRD5A2, Finasteride, LUTS
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 242 participants (estimated)
- Lead sponsor
- Beth Israel Deaconess Medical CenterUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- 3 Dec 2025 (actual)
- Primary completion
- 1 Jun 2029 (estimated)
- Study completion
- 31 Aug 2030 (estimated)
- First posted
- 25 Apr 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
SRD5A2 is a critical enzyme for prostatic development and growth, and the SRD5A2 inhibitor, finasteride, is used to treat benign prostatic hyperplasia (BPH). SRD5A2 is absent in 30% of normal adult men, which explains the resistance of a subset of patients to this commonly prescribed drug. This project proposes new combination therapies (5-ARI+raloxifene) and evaluates novel non-invasive biomarkers, based on alternative pathways that lead to prostatic enlargement.
Detailed description
Over 90% of adult males develop lower urinary tract symptoms (LUTS) secondary to bladder outlet obstruction by age 80 secondary to benign prostatic hyperplasia (BPH). BPH, the most common proliferative abnormality in humans, negatively impact the quality of life of 210 million men globally, accounting for significant life years lost. This study proposes to clinically evaluate the mechanisms of resistance to 5α-reductase inhibitor, finasteride, one of the more common drugs used to manage BPH and associated LUTS. Ongoing work has focused on steroid 5α-reductase 2 (SRD5A2, aka: 5α-reductase 2 [5AR2]), the enzyme responsible for prostatic development and growth. Investigations have revealed that expression of SRD5A2 is variable, and in fact, 30% of men do not express SRD5A2 in prostate tissues. Previous work, shows that somatic suppression of SRD5A2 during adulthood is dependent on epigenetic changes associated with methylation of the promoter region of the SRD5A2 gene. Studies indicate that (1) methylation of the SRDA2 is regulated by direct binding of the DNA-methyl transferase 1 (DNMT1) protein to the SRD5A2 promoter; (2) the inflammatory mediators TNF-α, NF-kB, and IL-6 regulate DNMT1 binding and subsequent methylation of the SRD5A2 promoter region; (3) clinical conditions associated with increased inflammation, age, and obesity, are associated with decreased expression of SRD5A via epigenetic modification; (4) in the absence of prostatic SRD5A2, alternate estrogenic pathways are upregulated, leading to an androgenic-to-estrogenic switch in the prostate gland, thus creating alternate pathways for prostatic growth. Therefore, it is hypothesized that (1) non- invasive assessment of SRD5A2 methylation status in peripheral blood can be an excellent indicator for resistance to 5ARI therapy, and (2) in men demonstrating hypermethylation of SRD5A2 and low protein expression (patients suspected of being resistant to 5ARI therapy), combination therapy (Selective Estrogen Receptor Modulators [SERMs]+5ARI) will serve as a better treatment strategy. To demonstrate the clinical significance of epigenetic changes to SRD5A2 and confirm its role in regulating sensitivity to 5ARI treatment, and to examine the role of estrogenic signaling blockade, a clinical trial is proposed with: Specific Aim 1: To assess the role of combination therapy (5ARI + SERM) in the treatment of BPH and to determine whether methylation of SRD5A2 promoter is a predictor for response to therapy. Specific Aim 2: To prospectively evaluate whether non-invasive radiologic prostate inflammatory markers can predict circulating WBCs SRD5A2 promoter methylation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Finasteride + Inactive Placebo Monotherapy | Active comparator | Drug: FinasterideParticipants may be randomized into the Finasteride + Inactive Placebo Monotherapy arm. |
| Finasteride + Raloxifene Combination Therapy | Experimental | Drug: raloxifene, Drug: FinasterideParticipants may be randomized into the Finasteride + Raloxifene Combination Therapy arm. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- ≥18 yrs old on the day of study consent;
- Finasteride has been recommended for treatment of BPH by a physician;
- PSA <20ng/ml within the last six months;
- Willingness to maintain any current genitourinary medications (e.g., beta agonists, alpha blockers, anticholinergics);
- Patient is able and willing to provide written informed consent.
Key exclusion criteria (16 listed)
- Active or past history of venous thromboembolism, including deep vein thrombosis, pulmonary embolism, and retinal vein thrombosis;
- Previous diagnosis with any prostatic malignancy or precancerous lesions (atypical glandular foci);
- History of pelvic radiation;
- Actively receiving intravesical therapy for bladder cancer;
- Received treatment with any demethylating medications (azacitidine, decitabine, zebularine, guadecitabine, hydralazine);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| raloxifeneParticipants in the Finasteride + Raloxifene Combination Therapy Arm will receive both Finasteride and Raloxifene as their intervention. Participants randomized to the Finasteride + Raloxifene Combination Therapy arm will self-administer finasteride at 5 mg orally/day and raloxifene at 60 mg orally/day. | Drug | Finasteride + Raloxifene Combination Therapy |
| FinasterideParticipants randomized to the Finasteride + Inactive Placebo Monotherapy arm will self-administer finasteride at 5 mg orally/day and placebo capsule daily. | Drug | Finasteride + Inactive Placebo Monotherapy, Finasteride + Raloxifene Combination Therapy |
Primary outcome
Clinical response to at 12 months after study enrollment
Time frame: From enrollment to the end of treatment at 12 months
The primary endpoint is the clinical response (yes-no) to therapy at 12 months after study enrollment between the combination and monotherapy treatment groups. Clinical response will be defined as ≥3-point decrease in International Prostate Symptom Score between baseline and the 12-month timepoint, adjusting for baseline measure of International Prostate Symptom Score. The minimal International Prostate Symptom Score is 0, denoting no symptoms, and the maximum score is 35, denoting severe symptoms.
5 secondary outcomes
Heterogeneity of clinical response to at 12 months after study enrollment by methylation score
Time frame: From enrollment to the end of treatment at 12 months
Comparison of mean International Prostate Symptom Score between study arms
Time frame: From enrollment to the end of treatment at 12 months
Comparison of mean International Index of Erectile Function Questionnaire scores between study arms
Time frame: From enrollment to the end of treatment at 12 months
Correlation between methylation and MRI scores
Time frame: From enrollment to the end of treatment at 12 months
Number of Participants with Treatment-Related Adverse Events as Assessed by CTCAE v5.0
Time frame: From enrollment to the end of treatment at 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Mar 2026.
- Individual participant dataSharing planned: Yes. All individual participant data collected throughout the trial. Data will be fully de-identified prior to sharing.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Aria Olumi, MD principal investigator
Beth Israel Deaconess Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing raloxifene and Finasteride in people with BPH (Benign Prostatic Hyperplasia) and Lower Urinary Track Symptoms, run by Beth Israel Deaconess Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 23 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Yulia Mulugeta (617-632-8890, ymuluget@bidmc.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical response to at 12 months after study enrollment (time frame: From enrollment to the end of treatment at 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Mar 2026.