Clinical trial NCT04522739: Spironolactone Safety in African Americans with Mild Cognitive Impairment and Early Dementia
Official title: Spironolactone Safety in African Americans with Mild Cognitive Impairment and Early Dementia
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Mild Cognitive Impairment
Alzheimer Disease
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Alzheimer's Association
First posted: 2020-08-21
Enrollment: 30
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Detailed description: In 2018, 5.5 million older adults in the United States were diagnosed with Alzheimer's disease, and it is predicted that 15 million people will be diagnosed with dementia, including Alzheimer's disease by 2060. Older African Americans adults are more likely to be diagnosed with Alzheimer's disease as compared to Whites. Research search studies on high blood pressure show that African Americans have higher levels of the hormone aldosterone that can be involved with regulation of blood pressure and blood vessels. Research studies also show that changes in blood vessels in the brain from higher aldosterone levels are related to changes in thinking skills and memory (cognition). Spironolactone is a drug that blocks aldosterone and has been used to treat high blood pressure for 60 years. More recently, this drug has shown to have the potential to decrease declines in thinking skills and memory.

Spironolactone is widely used in clinical practice and is well-tolerated by younger and older persons. As such, this study is designed to learn how a small group of older African American adults with mild cognitive impairment will tolerate the drug. Persons who are eligible for the study and agree to participate will receive spironolactone or a placebo and be monitored for drug side effects for one year.

During the study, the researchers will monitor changes in thinking and memory and blood vessel stiffness, in addition to side effects that may be related to the drug. Study tests include questionnaires that evaluate thinking skills and memory, and an ultrasound that measures the stiffness of blood vessels in the neck which deliver blood to the brain. The thinking and memory tests and ultrasound will be performed at the beginning of the study, then repeated at the end of the study.

The results of this study can justify a larger size study of spironolactone in older African Americans with mild cognitive impairment. The study has the potential to identify a new use for a well-known drug that is safe and widely used in current clinical practice. Further, the results from this study can address a racial difference in Alzheimer's disease and preserve the health of the brain as people age.

Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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
* Women of childbearing potential, i.e., non-menopausal
* When potential participants are not capable of providing informed consent due to their cognitive impairment and a study partner/legally authorized representative (LAR) is not available to sign consent forms on their behalf

Primary outcomes:
measure: Count of Adverse Events
timeFrame: Year 1
measure: Attrition rate
timeFrame: Year 1
Secondary outcomes:
measure: Change in Trail Making Test Part A Score
timeFrame: Baseline, Month 6, Month 12
measure: Change in Trail Making Test Part B Score
timeFrame: Baseline, Month 6, Month 12
measure: Change in Hopkins Verbal Learning Test-Revised (HVLT-R) Total Recall Score
timeFrame: Baseline, Month 6, Month 12
measure: Change in Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall Score
timeFrame: Baseline, Month 6, Month 12
measure: Change in Hopkins Verbal Learning Test-Revised (HVLT-R) Recognition Discrimination Index Score
timeFrame: Baseline, Month 6, Month 12
measure: Change in Digit Span Test Score
timeFrame: Baseline, Month 6, Month 12
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Emory Clinic at Executive Park
state: Georgia
Study officials:
affiliation: Emory University
name: Antoine Trammell, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References: