Spironolactone for Alzheimer's Disease

(STAND Trial)

Overseen By Antoine Trammell, MD, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Emory University

Must not be taking: RAAS modulators

Disqualifiers: Stroke, Renal disease, Hyperkalemia, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 12 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether the blood pressure medication spironolactone can assist with memory and thinking issues in older African American adults with mild cognitive impairment (MCI). Participants will take either spironolactone or a placebo for a year to determine if it enhances their memory and thinking skills. Individuals who identify as African American, have controlled blood pressure, and experience memory problems may be suitable candidates for this trial. As a Phase 4 trial, this research aims to understand how the already FDA-approved and effective treatment benefits a broader range of patients.

Do I need to stop my current medications to join the trial?

The trial requires that you do not take certain blood pressure medications, specifically those that affect the renin-angiotensin-aldosterone system (RAAS), like angiotensin II receptor blockers, ACE inhibitors, renin inhibitors, or aldosterone antagonists. If you are on these medications, you may need to stop them to participate.

What is the safety track record for spironolactone?

Research shows that spironolactone, a medication often used to treat high blood pressure, is generally safe and well-tolerated. It has been used in medical practice for many years. Studies with healthy individuals have shown that spironolactone can positively affect memory, particularly during stressful situations. While results have varied, researchers have not consistently found major safety concerns.

Currently, spironolactone is being tested in older adults with memory issues, and no specific safety problems have been identified so far. Since this trial is in a later stage, the treatment has already passed earlier safety tests. For those considering joining this trial, it is reassuring that spironolactone has a long history of use and is generally considered safe. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Spironolactone is unique because it's traditionally used as a diuretic, but now it's being explored for Alzheimer's due to its potential to target aldosterone, a hormone that might play a role in brain inflammation and cognitive decline. Unlike standard treatments for Alzheimer's, which mainly focus on boosting neurotransmitters like acetylcholine, spironolactone offers a new angle by possibly reducing brain inflammation. Researchers are excited about spironolactone because it could complement existing therapies and offer a novel approach to slowing down the progression of early Alzheimer's symptoms.

What evidence suggests that spironolactone might be an effective treatment for mild cognitive impairment?

Research suggests that spironolactone, a drug often used to treat high blood pressure, might also aid memory and thinking skills. Some studies have found that it can enhance memory related to understanding spaces and locations, especially under stress. It may also help slow memory and thinking problems over time. However, results are mixed, as spironolactone has shown limited effects in some situations. In this trial, participants will receive either spironolactone or a placebo. While spironolactone's impact on memory and thinking isn't fully proven, it shows promise in addressing memory issues. ^{1 2 3 5 6}

Who Is on the Research Team?

Antoine Trammell, MD, MPH

Principal Investigator

Emory University

Are You a Good Fit for This Trial?

This trial is for older African American adults with mild cognitive impairment or early Alzheimer's. Participants must be willing to follow the study procedures for a year, have certain blood pressure levels, and score within specific ranges on memory and thinking tests. It excludes those with severe medical issues, women who can become pregnant, recent stroke survivors, uncontrolled hypertension or heart failure.

Inclusion Criteria

Signed and dated informed consent form

I am willing and able to follow all study rules and attend all appointments.

My blood pressure meets the study's specific criteria.

Exclusion Criteria

I do not have kidney disease, high potassium, uncontrolled heart issues, or mental conditions affecting my thinking. My thyroid and vitamin B12 levels are normal.

My blood pressure is not well controlled.

I have difficulty understanding or following instructions.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive spironolactone or placebo for 12 months to assess tolerability and effects on cognitive function

12 months

4 to 5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including cognitive tests and ultrasound assessments

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Spironolactone

Trial Overview The trial is testing if spironolactone, a blood pressure medication, is safe for participants and if it affects their memory and thinking skills. Over one year, they'll take either spironolactone or a placebo while attending 4-5 study visits where their cognitive abilities will be assessed.

How Is the Trial Designed?

Group I: Spironolactone Experimental Treatment 1 Intervention

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

Group II: Placebo Placebo Group 1 Intervention

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

Spironolactone is already approved in United States, European Union for the following indications:

Approved in United States as Aldactone for:

• High blood pressure
• Heart failure
• Liver scarring
• Kidney disease
• Low blood potassium
• Early puberty in boys
• Acne
• Excessive hair growth in women

Approved in European Union as Aldactone for:

• Fluid retention due to heart failure
• Liver scarring
• Kidney disease
• High blood pressure
• Low blood potassium

Who Is Running the Clinical Trial?

Emory University

Lead Sponsor

Trials

1,735

Recruited

2,605,000+

Alzheimer's Association

Collaborator

Trials

103

Recruited

44,300+

Published Research Related to This Trial

The study successfully isolated three known and five new steroidal impurities from spironolactone using various chromatographic methods, enhancing our understanding of the compound's composition.

The structures of the new compounds were elucidated through spectrometric analysis, providing valuable insights into their chemical properties and potential implications for the safety and efficacy of spironolactone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Isolation and identification of novel impurities in spironolactone. Chen, H., Wang, YF., Yang, ZD., et al.[2013]

A new steroidal compound, the 15 beta,16 beta-methylene derivative 17, was developed and showed twice the aldosterone antagonistic potency compared to the standard drug spironolactone.

This new compound also demonstrated significantly reduced antiandrogenic side effects, suggesting it could be a safer alternative for patients needing aldosterone antagonism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aldosterone antagonists. 3. Synthesis and activities of steroidal 7 alpha-(alkoxycarbonyl)-15,16-methylene spirolactones. Nickisch, K., Bittler, D., Laurent, H., et al.[2019]

Allopregnanolone was found to be safe and well tolerated in a trial involving 24 participants with early Alzheimer's disease, with no significant adverse events related to the treatment, indicating its potential as a therapeutic option.

The study established a maximum tolerated dose (MTD) for allopregnanolone, with pharmacokinetic data showing a predictable linear dose-response, supporting further investigation into its efficacy for Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety, tolerability, and pharmacokinetics of allopregnanolone as a regenerative therapeutic for Alzheimer's disease: A single and multiple ascending dose phase 1b/2a clinical trial. Hernandez, GD., Solinsky, CM., Mack, WJ., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04522739

Study Details | Spironolactone Safety in African Americans ... 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 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11856062/

Mineralocorticoid Receptor Antagonists and Cognitive ... Results: Spironolactone demonstrated mixed effects on cognition. In healthy participants, it improved spatial memory under stress and prevented ...

3. trialx.com trialx.com/clinical-trials/listings/265614/spironolactone-safety-in-african-americans-with-mild-cognitive-impairment-and-early-alzheimers-disease/

Spironolactone Safety in African Americans With Mild ... 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 ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04522739/spironolactone-safety-in-african-americans-with-mild-cognitive-impairment-and-early-dementia

Spironolactone Safety in African Americans with Mild ... More recently, this drug has shown to have the potential to decrease declines in thinking skills and memory.

5. researchgate.net researchgate.net/publication/355453543_The_Effect_of_Spironolactone_on_b-amyloid-Induced_Memory_Impairment_in_Male_Rats_The_Role_of_Microglial_Inhibition

(PDF) The Effect of Spironolactone on β-amyloid-Induced ... Conclusion: Spironolactone had a modulatory effect on neuroinflammation through a repressive effect on microglial activation with no valuable effect on memory ...

6. peearz.com peearz.com/trialsindex?nctid=NCT04522739

Spironolactone Safety in African Americans With Mild ... This study will also investigate the effect of spironolactone on memory and thinking abilities as measured by performance on cognitive tests, which are tests ...