Data Analysis for Drug Repurposing for Effective Alzheimer's Medicines (DREAM) - PDE5

Data Analysis for Drug Repurposing for Effective Alzheimer's Medicines (DREAM)- PDE5

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: Completed
• Conditions: Pulmonary Arterial Hypertension
• Intervention / Treatment: Drug: PDE5 inhibitor; Drug: Endothelin Receptor Antagonists

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): 13021

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: 65 years and older (Older Adult)
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

This study will employ a new user, active comparator, observational cohort study design comparing PDE5 inhibitors (sildenafil, tadalafil) to endothelin receptor antagonists (bosentan, ambrisentan, macitentan). The patients will be required to have continuous enrollment during the baseline period of 365 days before initiation of study drugs (cohort entry/index date). Follow-up for the outcome (dementia) differs between analyses. Follow-up begins the day after drug initiation (analysis 1, 3, 4); 180 days after drug initiation (analysis 2).

Description

Please see https://docs.google.com/spreadsheets/d/19NwmDi8xwWjzXqhSLPDTg4CKHt5UDQXuwCnZwY8jCS8/edit?usp=sharing or Appendix A for full code and algorithm definitions.

Medicare timeframe: 2008 to 2018 (end of data availability).

Inclusion Criteria:

• 1. Aged > 65 years on the index date
• 2. No prior use of PDE5 inhibitors (sildenafil, tadalafil) and endothelin receptor antagonists (bosentan, ambrisentan, macitentan) anytime prior to cohort entry date
• 3. 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 pulmonary arterial hypertension 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?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
PDE5 inhibitors; Exposure group	Drug: PDE5 inhibitor; PDE5 inhibitors (sildenafil, tadalafil) claim is used as the exposure group.
Endothelin receptor antagonists; Reference group	Drug: Endothelin Receptor Antagonists; Endothelin receptor antagonists (bosentan, ambrisentan, macitentan) 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 includes: 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. Analysis 1-'as-treated' follow-up approach: In this approach, we followed patients from cohort entry until treatment discontinuation or switch to the comparator treatment, insurance disenrollment, death, or administrative endpoint (December 2018). Treatment discontinuation was defined as occurring 90 days after the expected days supply. of the most recently filled prescription to accommodate suboptimal adherence during treatment periods. Analysis 2-'as-started' follow-up approach incorporating a 6-month 'induction' period. Analysis 3-incorporating a 6-month 'symptoms to diagnosis' period Analysis 4-high-specificity outcome definition Study accessed Medicare files (Jan 2008-Dec 2018) between September 1, 2021 to October 4, 2022.	Median follow up times: 1) 168 days (exp), 151 days (ref) 2) 693 days (exp), 720 days (ref) 3) 382 days (exp), 358 days (ref) 4) 169 days (exp), 151 days (ref)

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 242 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): September 1, 2021
• Primary Completion (Actual): September 30, 2021
• Study Completion (Actual): October 4, 2022

Study Registration Dates

• First Submitted: September 1, 2021
• First Submitted That Met QC Criteria: September 1, 2021
• First Posted (Actual): September 9, 2021

Study Record Updates

• Last Update Posted (Actual): August 6, 2025
• Last Update Submitted That Met QC Criteria: July 25, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Hypertension, Pulmonary; Pulmonary Arterial Hypertension; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Phosphodiesterase Inhibitors; Endothelin Receptor Antagonists; Phosphodiesterase 5 Inhibitors
• Other Study ID Numbers: 2019A010961-8

Drug and device information, study documents

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