5-Alpha Reductase 2 as a Marker of Resistance to 5ARI Therapy

NCT04288427 | Recruiting

• 2 other identifiers: 2020P000202R01DK124502
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The study is being conducted to learn why some patients with Benign Prostatic Hyperplasia (BPH) do not respond to a commonly used treatment drug, Finasteride. The hope is to find ways to predict which patients will not respond to Finasteride so that, in the future, these patients can be identified prior to offering this treatment and they can be offered alternative treatment strategies in its place. The aim is to see if noninvasive techniques such as MRI can detect inflammation of the prostate to assist with early detection of those who will and who will not respond to Finasteride.

Conditions

Benign Prostatic Hyperplasia; Prostate Hyperplasia; Prostate Disease; Prostate Hypertrophy; Prostate Pain; Lower Urinary Tract Symptoms; Urinary Obstruction; Urinary Tract Disease

Keywords

Finasteride; 5 Alpha Reductase

Outcome Measures

Primary Outcomes (1)

• Finasteride treatment effect on lower urinary tract symptom improvement by urinary symptom score

  Validated questions of the AUA Urinary Symptom Score will be used every 6 months to assess efficacy of Finasteride treatment in improving lower urinary tract symptoms in the patient population. Based on previous randomized trials, it will be determined whether the patient is responsive or resistant to the treatment dependent on changes in their AUA Urinary Symptom Score at the first 12 month mark. For patients who are resistant to Finasteride, other medical or surgical treatments will be offered, and the patients will be removed from the study.

  Assessment of Finasteride responsiveness through changes in urinary symptoms will be completed at 6 month intervals during clinic visits, and treatment efficacy will be determined after the first 12 months.

Study Arms (1)

Finasteride Treatment

EXPERIMENTAL

Patients who are eligible will be given 5ARI therapy, Finasteride, for medical management of Benign Prostatic Hyperplasia (BPH) symptoms. Only patients with lower urinary tract symptoms (LUTS) as assessed by American Urologic Association (AUA) urinary symptom score \> than 8, (suggestive of moderate LUTS) prostate size \> 40cc, no prostate nodule/tenderness/firmness and increased PSA between 4-10ng/ml requiring prostate biopsy will be enrolled. Then, they will have prostate MRIs/needle biopsies and blood/urine collection followed by treatment with Finasteride (standard of care). They will be followed in urology clinic for assessment of LUTS every 6 months and Finasteride responsiveness at the 12-month time point. Prostate biopsy samples will be evaluated for SRD5A2 gene expression/methylation, hormonal androgen/estrogen levels (which will be repeated in blood samples). Prostate MRIs will assess size/inflammatory changes at the start and 3-year time points.

Drug: Finasteride

Interventions

Finasteride DRUG

Patients who are candidates to receive 5ARI therapy, Finasteride, for clinical medical management of lower urinary tract symptoms will begin treatment once deemed eligible. They will be assess every 6 months for changes in urinary symptom scores and their responsiveness to the Finasteride treatment will be assessed at the 12-month time point. MRIs of prostate taken at the start of study and at the 3 year time point will assess prostate size and changes in size as well as degree of inflammatory changes. Gene expression of SRD5A2 as well as methylation pattern will be tested on prostate tissue samples, where hormonal androgen/estrogen levels will also be assessed as they are in blood samples.

Also known as: Sequential Time Point Study

Finasteride Treatment

Eligibility Criteria

• Age: 50 Years+
• Gender Eligibility Details: Prostatic disease are limited to biologically male individuals.
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male (physiological);
• Age ≥ 50;
• Eligible for treatment with 5ARI therapy;
• Presence of lower urinary tract symptoms secondary to BPH;
• Prostate size \>40cc by digital rectal examination;
• Absence of prostate nodule, tenderness or firmness;
• Mildly elevated PSA's \>1.5 ng/ml and ≤ 40 ng/ml;
• Undergoing clinically indicated prostate biopsy for elevated prostate-specific antigen (PSA).

You may not qualify if:

• Diagnosis of any prostatic malignancy or precancerous lesions (atypical glandular foci and prostatic intraepithelial neoplasia);
• Treatment with 5ARI (Finasteride or Dutasteride) within six months of study enrollment;
• Current urinary tract infection;
• Previous pelvic radiation;
• Previous treatment with demethylating drugs;
• Diagnosis of multiple sclerosis, Alzheimer's, Parkinson's, neurological deficits in the judgment of the investigator;
• Unable or unwilling to undergo MRI due to implants, claustrophobia, etc.

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

RECRUITING

Related Publications (22)

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MeSH Terms

Conditions

Prostatic Hyperplasia; Prostatic Diseases; Lower Urinary Tract Symptoms; Urologic Diseases

Interventions

Finasteride

Condition Hierarchy (Ancestors)

Genital Diseases, Male; Genital Diseases; Urogenital Diseases; Male Urogenital Diseases; Urological Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications

Intervention Hierarchy (Ancestors)

Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Azasteroids; Steroids, Heterocyclic

Study Officials

• Aria F. Olumi, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Yulia Mulugeta, BS

CONTACT

617-632-8890; ymuluget@bidmc.harvard.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator; Chief of Urologic Surgery at Beth Israel Deaconess Medical Center; Janet & William DeWolf Professor of Surgery/Urology at Harvard Medical School; American Urological Association Chair of Research

Study Record Dates

• First Submitted: February 10, 2020
• First Posted: February 28, 2020
• Study Start: September 25, 2020
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: October 28, 2025

Record last verified: 2025-10

Locations

US (1)