Data Analysis for Drug Repurposing for Effective Alzheimer's Medicines - (DREAM) Probenecid vs Allopurinol

Data Analysis for Drug Repurposing for Effective Alzheimer's Medicines- Probenecid vs Allopurinol

This study aims to evaluate the comparative risk of dementia/Alzheimer's disease onset between patients treated with medications that target specific metabolic pathways and patients treated with alternative medications for the same indication.

Study Overview

• Status: Active, not recruiting
• Conditions: Gout
• Intervention / Treatment: Drug: Probenecid; Drug: Allopurinol

Detailed Description

This is a non-randomized, non-interventional study that is part of the DREAM Study of Brigham and Women's Hospital. DREAM is led by Dr. Madhav Thambisetty, MD, PhD, Chief of the Clinical and Translational Neuroscience Section, Laboratory of Behavioral Neuroscience, National Institute on Aging (NIA) intramural research program. This study aims to evaluate the comparative risk of dementia/Alzheimer's disease onset between patients treated with medications that target specific metabolic pathways and patients treated with alternative medications for the same indication using healthcare claims data.

• Study Type: Observational
• Enrollment (Actual): 294878

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02120
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

This study will involve a new user, parallel group, cohort study design comparing probenecid to allopurinol. The patients will be required to have continuous enrollment during the baseline period of 365 days before initiation of probenecid or allopurinol (cohort entry date). Follow-up for the outcome (incident dementia), begins the day after drug initiation for analyses 1, 3, and 4 and 180 days after drug initiation for analysis 2.

Description

Please see https://docs.google.com/spreadsheets/d/1N3IVoirGdWS7OiKiOWWgPHhgsSxX7SWDIhpeeZ-Ft7c/edit?usp=sharing or Appendix A for full code and algorithm definitions.

Medicare timeframe: 2007 to 2017 (end of data availability).

Inclusion Criteria:

• 1. No prior use of urate-lowering agents, including probenecid and allopurinol anytime prior to cohort entry date
• 2. Enrollment in Medicare Part A, B, and D with no HMO coverage for 365 days prior to and including cohort entry date

Exclusion Criteria:

• 1. Prior history of dementia measured anytime prior to cohort entry date
• 2. No prior history of gout recorded in the 365 days prior to cohort entry date
• 3. Prior history of nursing home admission in the 365 days prior to the cohort entry date

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Probenecid; Exposure group	Drug: Probenecid; Probenecid claim is used as the exposure group.
Allopurinol; Reference group	Drug: Allopurinol; Allopurinol claim is used as the reference group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to dementia onset	Time to dementia onset, i.e., Alzheimer's disease, vascular dementia, senile, presenile, or unspecified dementia, or dementia in other diseases classified elsewhere. Please refer to uploaded protocol for full definition due to size limitations.	Through study completion (a median of 243 days)]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to Alzheimer's disease onset	Time to Alzheimer's disease onset. Please refer to uploaded protocol for full definition due to size limitations.	Through study completion (a median of 243 days)]

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: Johns Hopkins University; National Institute on Aging (NIA); Rutgers University
• Investigators: Principal Investigator: Madhav Thambisetty, MD, PhD, National Institute on Aging (NIA)

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2021
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: February 5, 2021
• First Submitted That Met QC Criteria: February 5, 2021
• First Posted (Actual): February 10, 2021

Study Record Updates

• Last Update Posted (Actual): July 18, 2023
• Last Update Submitted That Met QC Criteria: July 17, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Antimetabolites; Protective Agents; Antioxidants; Free Radical Scavengers; Gout Suppressants; Uricosuric Agents; Allopurinol; Probenecid
• Other Study ID Numbers: 2019A010961-5; 75N95019C00057 (Other Grant/Funding Number: National Institute on Aging)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No