Spironolactone Safety in African Americans With Mild Cognitive Impairment and Early Dementia

NCT04522739 | Completed Phase 4 DMC FDA Drug

• 1 other identifier: STUDY00000124
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate whether a blood pressure medication, spironolactone, can be tolerated by older African American adults that have memory and thinking problems, also called mild cognitive impairment (MCI). This study will also investigate the effect of spironolactone on memory and thinking abilities as measured by performance on cognitive tests, which are tests that measure memory and thinking skills. Participants will take spironolactone or a placebo for one year and will have 4 to 5 study visits during the study period.

Conditions

Mild Cognitive Impairment; Alzheimer Disease

Outcome Measures

Primary Outcomes (2)

• Count of Adverse Events

  The safely of the study treatment will be assessed with the number of adverse events experienced in each study arm.

  Year 1

• Attrition rate

  The tolerability of the study treatment will be assessed by the attrition rate of participants in each study arm.

  Year 1

Secondary Outcomes (6)

• Change in Trail Making Test Part A Score

  Baseline, Month 6, Month 12

• Change in Trail Making Test Part B Score

  Baseline, Month 6, Month 12

• Change in Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall Score

  Baseline, Month 6, Month 12

• Change in Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall Score

  Baseline, Month 6, Month 12

• Change in Hopkins Verbal Learning Test-Revised (HVLT-R) Recognition Discrimination Index Score

  Baseline, Month 6, Month 12

Study Arms (2)

Spironolactone

EXPERIMENTAL

Participants with mild cognitive impairment or early Alzheimer's Disease who are randomized to receive spironolactone for 12 months.

Drug: Spironolactone

Placebo

PLACEBO COMPARATOR

Participants with mild cognitive impairment or early Alzheimer's Disease who are randomized to receive a placebo to match spironolactone for 12 months.

Drug: Placebo

Interventions

Spironolactone DRUG

Study participants will receive a 25 mg dose of spironolactone. Participants will take one capsule by mouth per day for 12 months.

Also known as: Aldactone

Spironolactone

Placebo DRUG

A placebo to match spironolactone will be taken orally once per day for 12 months.

Placebo

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated informed consent form
• Willingness to comply with all study procedures and availability for the duration of the study
• Self-identified African American
• Blood pressure (BP) and hypertension criteria: normotensive and hypertensive participants will be eligible
• Normotensive criteria: BP 110-140/40-90 mmHg and not receiving any treatment for hypertension
• Hypertensive criteria: only controlled hypertensives will be eligible with BP range as in the normotensive criteria of 110-140/40-90 mmHg
• MCI defined as:
• Abnormal memory function per the Logical Memory subscale (Delayed Paragraph Recall, Paragraph A only) from the Wechsler Memory Scale-Revised (the maximum score is 25):
• Score \<11 for 16 or more years of education
• Score \<9 for 8-15 years of education
• Score \<6 for \<7 years of education
• Montreal Cognitive Assessment (MoCA) score 13-25
• Preserved general functional performance per Functional Assessment Questionnaire (FAQ)\<9

You may not qualify if:

• History of stroke in the previous three years
• MoCA\<13 or the inability to follow instructions to perform cognitive testing
• Inability to participate in the study procedures: cognitive tests (communication limitations from language or other factors)
• Active medical problem/symptom that interferes with the study procedures, e.g., chest pain, shortness of breath, or abdominal pain
• Deemed ineligible by study investigators due to safety issues or non-compliance
• History of the inability to tolerate treatment with an aldosterone antagonist
• Hypertension
• Uncontrolled defined as a BP \> 140/90 mmHg
• Current therapy with RAAS modulating medications, i.e., angiotensin II receptor blocker (ARB), angiotensin converting enzyme inhibitor (ACEi), renin inhibitor, or aldosterone antagonist such as eplerenone (Inspra) due to the risk of hyperkalemia and the interference with the renin angiotensin aldosterone system (RAAS) system
• Renal disease (baseline creatinine \> 2.0 mg/dL)
• Hyperkalemia (K+ \> 5.5 milliequivalent (mEq)/dL)
• Other neurological or psychiatric conditions that could impact cognition, e.g., Parkinson's disease and related movement disorders, multiple sclerosis, epilepsy, or schizophrenia, untreated major depressive disorder, and other psychotic disorders
• Abnormal thyroid stimulating hormone (TSH) (\>10 milliunits (mU)/L) or vitamin B12 (\<250 pg/mL) as they can impact cognitive function. If the potential participant's TSH and/or vitamin B12 levels are abnormal, then the PI may enroll that person if it is thought the lab abnormalities are unrelated and do not affect cognitive function
• Active medical or psychiatric disease, which in the judgment of the study investigators affects participant safety or the scientific integrity of the study
• Uncontrolled congestive heart failure reflected by poor exercise tolerance and shortness of breath

Sponsors & Collaborators

• Emory University: lead
• Alzheimer's Association: collaborator

Study Sites (1)

Emory Clinic at Executive Park

Atlanta, Georgia, 30329, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction; Alzheimer Disease

Interventions

Spironolactone

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Antoine Trammell, MD, MPH

  Emory University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: August 19, 2020
• First Posted: August 21, 2020
• Study Start: September 6, 2022
• Primary Completion: September 23, 2025
• Study Completion: September 23, 2025
• Last Updated: October 29, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: The data will become available beginning 36 months and ending three years following article publication.
• Access Criteria: The data will be shared with researchers who provide a methodically sound proposal in order to achieve aims in the approved proposal. Proposals may be submitted up to 36 months following article publication. After 36 months, the data will be available in Emory University's data warehouse but without investigator support other than deposited metadata. Proposals should be directed to antoine.trammell@emory.edu. The requestors will need to sign a data access agreement to gain access to the data.

Locations

US (1)