Evaluate the Effect of Atorvastatin on Cerebrovascular Reactivity in Mild Cognitive Impairment (MCI)

Targeting Cerebrovascular Reactivity for Precision Medicine: Pilot Trial of Atorvastatin

The purpose of this study is to evaluate the effect of atorvastatin on brain vessel reactivity and with it on blood flow in people with mild cognitive impairment.

Study Overview

• Status: Recruiting
• Conditions: Mild Cognitive Impairment
• Intervention / Treatment: Drug: Atorvastatin Oral Tablet

Detailed Description

Participants are first being informed about potential benefits and risks of the study and are required to give written consent. After that participants will undergo detailed phone screen to determine eligibility for study entry. At week 0, participants who meet eligibility requirements will be prescribed atorvastatin (40 mg, once in the evening) in an open-label manner.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Ritu Agarwal; Phone Number: 410-550-9020; Email: ragarw19@jhmi.edu
• Study Contact Backup: Name: Samantha Horn; Phone Number: 410-550-9020; Email: shorn8@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Recruiting
      • Johns Hopkins University, Bayview Medical Center
      • Contact: Ritu Agarwal; Phone Number: 410-550-9020; Email: ragarw19@jhmi.edu
      • Principal Investigator: Paul Rosenberg, MD
      • Contact: Samantha Horn; Phone Number: 410-550-9020; Email: shorn8@jhmi.edu
      • Sub-Investigator: Sevil Yasar, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 95 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria are chosen to include participants with MCI, enriched for vascular risk factors:

• MCI defined by Clinical Dementia Rating (CDR) of 0.5 or 1.0.
• Memory, processing speed, executive function, language - cognitive scores > 1.5 standard deviations below age-education norms.
• Not demented by history.
• Not taking statins currently or in the last 6 months.
• Cognitive/functional impairment not likely due to another neurological disease or delirium.

Exclusion Criteria:

• Taking a statin currently or have taken a statin in the last 6 months.
• Contraindications to taking a statin.
• Transplant patient taking cyclosporine.
• Unable to undergo MRI procedures (such as having an implanted pacemaker or defibrillator or stimulator or having non MRI compatible metal).
• Diagnosis of dementia by history.
• Current diagnosis of substance abuse.
• History of stroke or myocardial infarction in past 6 months.
• History of HIV.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Atorvastatin 40 mg; Participants receive 40 mg atorvastatin orally daily in the evening.	Drug: Atorvastatin Oral Tablet; Atorvastatin pill 40 mg to be taken every night; Other Names: Lipitor oral tablet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of MRI whole brain cerebrovascular reactivity (wbCVR)	MRI based CVR is a newer technique that measures dilatory function of the microvessels which have been shown to be superior to measurement of Cerebral blood flow (CBF) and have also been shown to be low in participants with MCI.	Baseline and 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in plasma exosomes	Endothelial-derived exosomes (EDE) reflect the neurochemistry of cerebrovascular endothelial cells, while neuronal-enriched extracellular vesicles (nEV) are associated with brain white matter hyperintensities.	Baseline and 12 weeks
Change in cognitive function (global neurocognitive measure)	Assessed by Global neurocognitive measure.	Baseline and 12 weeks
Change in cognitive function (domain-specific neurocognitive measure)	Assessed by Domain-specific neurocognitive measure.	Baseline and 12 weeks

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: The Richman Family Precision Medicine Center of Excellence in Alzheimer Disease
• Investigators: Principal Investigator: Paul Rosenberg, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): May 21, 2021
• Primary Completion (Estimated): July 31, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: February 18, 2021
• First Submitted That Met QC Criteria: February 18, 2021
• First Posted (Actual): February 21, 2021

Study Record Updates

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

More Information

Terms related to this study

• Keywords: Cerebral Vascular Reactivity
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Atorvastatin
• Other Study ID Numbers: IRB00256402

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes