BackgroundThe COVID-19 pandemic and the halt to in-person research activities beginning in March 2020 brought new challenges to protocol development and implementation. Due to the pandemic, we had to revise our protocol for the Brain Relationships Among Information, Neuroprocessing, and Self-Management (BRAINS) study, which was designed to examine health information behavior, brain activity, diabetes status, and self-management behavior among Black women with hypertension.ObjectiveThis report outlines 7 steps describing how our research team (1) revised the BRAINS study protocol, (2) implemented a remote method of data collection, and (3) mitigated the challenges we faced.MethodsPrior to March 2020, Black women with hypertension were invited to participate in the BRAINS study to undergo a functional magnetic resonance imaging scan, complete surveys, have their blood pressure measured, and have their blood drawn. After these measures were collected, participants would receive phone calls from a dietician to complete two 24-hour dietary recalls using the Nutrition Data System for Research. Our revised protocol relied on a web-based, interactive approach. Participants received a study kit that included an Omron automatic home blood pressure monitor and a hemoglobin A1ckit from the DTIL laboratory. In a Zoom meeting with each participant, our team played an introductory video, administered surveys (via Qualtrics), and guided participants through measuring their blood pressure and performing a finger stick to collect a blood sample for hemoglobin A1ctesting. We examined cognitive function using the TestMyBrain Digital Neuropsychology Toolkit, as we were unable to access the functional magnetic resonance imaging laboratory to assess brain activity. The 7 steps in revising our protocol were as follows: conceptualizing the move from in-person to remote study activities (step 1); contacting the funders (step 2); submitting changes for Institutional Review Board approval (step 3); preparing to implement the revised protocol (step 4); implementing the study changes (step 5); mitigating challenges (step 6); and evaluating protocol implementation (step 7).ResultsApproximately 1700 individuals responded to web-based advertisements about the BRAINS study. A total of 131 individuals completed our eligibility screener. We conducted our first Zoom appointment in July 2020 and our last Zoom appointment in September 2020. Using our revised strategies, a total of 99 participants completed all study measures within a 3-month period.ConclusionsIn this report, we discuss successes and challenges in revising our protocol and reaching our population of interest remotely, safely, and effectively. The information we have outlined can help researchers create similar protocols to reach and conduct research remotely with diverse populations, such as individuals who are unable to participate in studies in person.International Registered Report Identifier (IRRID)DERR1-10.2196/43849