PERSONAL: Feasibility Study Protocol for Placebo-Controlled, Randomized n-of-1 Trials of Tamsulosin for Lower Urinary Tract Symptoms

Abstract

Background: Lower urinary tract symptoms (LUTS) affect more than half of men over age 70 and contribute to both poor health-related quality of life and polypharmacy. Tamsulosin hydrochloride, a selective α₁-blocker, is the most common medication used to treat LUTS due to presumed benign prostatic hyperplasia and is often prescribed indefinitely, although not all men benefit from long-term therapy. N-of-1 trials allow for individualized estimates of benefit and harm and could facilitate decisions regarding chronic tamsulosin therapy for LUTS, particularly among older men. Our team developed the PERSONAL (PlacEbo-controlled, Randomized, patient-Selected Outcomes, N-of-1 triALs) app to track daily urinary symptoms and medication side effects for n-of-1 trials among older men with LUTS. Materials and Methods: We will conduct a feasibility study of 20 individual randomized n-of-1 trials using the PERSONAL app to compare tamsulosin (0.4 or 0.8 mg) vs. placebo among older men taking tamsulosin for LUTS. We will include men over age 65 with a smartphone for whom temporary discontinuation of tamsulosin is safe, (e.g., no history of acute retention). Participants will work with research staff to prospectively identify the most important urinary symptoms and medication side effects that they would like to digitally track. Men will then be randomized to 2-week treatment periods of tamsulosin or placebo followed by a 1-week wash-out with placebo, for 4 distinct treatment periods and 3 wash-out periods, totaling 11 weeks. Study medications will be blinded using over-encapsulation of tamsulosin pills and matching placebo. Our primary outcomes for this study will be recruitment and retention of eligible men, completion rates of n-of-1 trials and daily questionnaires using the PERSONAL app, and participants' perceived usefulness of their n-of-1 trial for determining whether tamsulosin is effective for them. Linear mixed effects models with individual-specific intercepts and intervention effects will also be used to estimate within-individual effects of tamsulosin. Discussion: The goal of this innovative study is to establish feasibility and acceptability of using a mobile health app and n-of-1 trials to provide older men with individualized estimates of benefits and harms of chronic tamsulosin therapy for LUTS.

Keywords: benign prostatic hyperplasia; deprescribing; medication side effects; patient-reported outcomes; personalized medicine; randomized clinical trial design; α-antagonist.

Figure 1

Study flow diagram. EHR electronic health record; IRB institutional review board; HIPPA Health Insurance Portability and Accountability Act.

Figure 2

Individual n-of-1 trial.

Figure 3

PERSONAL app screenshots. Screenshots demonstrate the PERSONAL app login page (A), selecting urinary symptoms for daily tracking (B), setting a daily questionnaire reminder (C), completing the daily questionnaire (D), the PERSONAL app home page with current and future tasks (E), and graphical representation of participant data (F).