Senicapoc for Alzheimer's Disease

(Senicapoc Trial)

Recruiting at 1 trial location

Overseen By Selene Leal Carrillo

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, Davis

Must be taking: Cholinesterase inhibitors, Memantine

Must not be taking: Benzodiazepines, Antipsychotics, Narcotics, Anti-epileptics

Disqualifiers: Unstable illnesses, Psychiatric illness, Drug abuse, others

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

Compensation: Varies

Number of Visits: 5

Duration: 52 weeks

55 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the drug Senicapoc might slow early symptoms of Alzheimer's disease, which affects memory and thinking. The researchers aim to determine if Senicapoc can improve cognitive function and reduce brain inflammation. Participants will receive either Senicapoc or a placebo (a substance with no active drug) for a year. Individuals with mild memory issues, diagnosed with early-stage Alzheimer's, may be suitable for this study. As a Phase 2 trial, the research focuses on assessing the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

The trial requires that you stop using certain medications like benzodiazepines, antipsychotics, narcotics, or anti-epileptic drugs, unless approved by the Principal Investigator. You can continue stable doses of cholinesterase inhibitors, memantine, and anti-depressants. If you take CNS active medications, you may need to skip doses before certain visits.

Is there any evidence suggesting that Senicapoc is likely to be safe for humans?

Research shows that senicapoc has been tested for safety in humans. Previous studies indicate that senicapoc is generally safe and well-tolerated. Although it didn't achieve its main goals in some studies, it did not cause serious side effects. This suggests it could be a safe option for further testing in Alzheimer's disease. The current trial phase suggests that serious safety concerns are unlikely, as this phase often focuses on human tolerance of the treatment. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Senicapoc is unique because it targets a different mechanism than most current Alzheimer's treatments. While many existing drugs for Alzheimer's focus on managing symptoms by boosting neurotransmitters like acetylcholine, Senicapoc works by blocking a specific potassium channel, which may help protect brain cells from stress and damage. This novel approach offers hope for not only slowing down the progression of the disease but potentially modifying its course. Researchers are excited about Senicapoc because it opens up a new pathway for tackling Alzheimer's, offering a fresh avenue of hope for patients and families dealing with this challenging condition.

What evidence suggests that Senicapoc might be an effective treatment for Alzheimer's disease?

Research has shown that Senicapoc might help treat Alzheimer's disease. Studies in mice found that Senicapoc can reduce brain swelling and decrease amyloid plaques, which are linked to Alzheimer's symptoms. This drug also penetrates the brain effectively, which is crucial for its efficacy. While promising data from animal studies exist, information from human studies remains limited. In this trial, participants will receive either 10 mg of Senicapoc daily or a placebo for 52 weeks. These early findings suggest that Senicapoc might help slow memory and thinking problems in people with Alzheimer's. ^{1 3 6 7 8}

Who Is on the Research Team?

John Olichney, MD

Principal Investigator

University of California, Davis

Are You a Good Fit for This Trial?

This trial is for people aged 55-85 with early Alzheimer's or mild cognitive impairment, fluent in English/Spanish, and have a study partner. Women must use contraception if of childbearing potential. Exclusions include pregnancy, difficulty swallowing pills, recent high radiation exposure, inability to undergo MRI scans, unstable medical conditions like severe heart failure or renal insufficiency, psychiatric illness history including major depression within the last two years.

Inclusion Criteria

I have someone who sees me at least 6 hours a week and can provide information about me.

Your test score on the Montreal Cognitive Assessment (MoCA) at the Screening visit needs to be between 15 and 28 after considering your level of education.

I am willing to possibly receive a placebo instead of the active drug.

Exclusion Criteria

You have a shunt or catheter implanted in your brain for draining fluid.

I take daily medication to prevent blood clots.

You have struggled with alcohol or drug problems in the last 5 years.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 10 mg daily Senicapoc or placebo for 52 weeks

52 weeks

Visits at baseline, weeks 4, 12, 26, 36, 52

Follow-up

Participants are monitored for safety and effectiveness after treatment, including a visit at 78 weeks to assess long-term effects

26 weeks

1 visit (in-person) at 78 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Senicapoc

Trial Overview The trial tests Senicapoc against a placebo in patients with mild Alzheimer's over one year. It aims to see if Senicapoc can improve cognition and reduce neuroinflammation by measuring changes in ADAS-Cog scores and inflammatory markers in blood/CSF.

How Is the Trial Designed?

Group I: 10 mg daily Senicapoc Experimental Treatment 1 Intervention

10 mg daily Senicapoc for 52 weeks

Group II: Placebo Group Placebo Group 1 Intervention

Placebo daily for 52 weeks

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

Alzheimer's Drug Discovery Foundation

Collaborator

Trials

22

Recruited

3,100+

Alzheimer's Association

Collaborator

Trials

103

Recruited

44,300+

Biossil Inc.

Industry Sponsor

Trials

1

Recruited

350+

Published Research Related to This Trial

Current Alzheimer's disease treatments mainly focus on improving symptoms rather than halting disease progression, with only selegiline and vitamin E showing any delay in important clinical endpoints.

Research is ongoing for new treatments aimed at slowing progression or preventing onset, including antioxidants, anti-inflammatory agents, and drugs targeting amyloid deposition, with trials also focusing on preventing Alzheimer's in individuals with mild cognitive impairment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Trials to slow progression and prevent disease onset. Thal, LJ.[2019]

A novel protein kinase C (PKC) activator, benzolactam (BL), significantly increased the secretion of non-amyloidogenic soluble APP (sAPP) in fibroblasts from Alzheimer's disease (AD) patients, suggesting a potential therapeutic approach to reduce harmful amyloid-beta production.

The effects of BL were confirmed to be PKC-dependent, as a PKC inhibitor eliminated the increase in sAPP secretion, indicating that enhancing PKC activity could favor healthier processing of the amyloid precursor protein in AD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benzolactam (BL) enhances sAPP secretion in fibroblasts and in PC12 cells. Ibarreta, D., Duchén, M., Ma, D., et al.[2019]

In a study of 210 patients with mild to moderate Alzheimer's disease, the 800 mg dose of tarenflurbil taken twice daily showed significant benefits in slowing decline in daily activities and global function for patients with mild AD, compared to placebo.

Tarenflurbil was well tolerated over 24 months, but it had no significant positive effects on cognitive decline in patients with moderate AD and even showed a negative impact on global function in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tarenflurbil in mild to moderate Alzheimer's disease: a randomised phase II trial. Wilcock, GK., Black, SE., Hendrix, SB., et al.[2016]

In Alzheimer's disease patients, levels of the protective protein PKCε are significantly lower in the brain compared to age-matched controls, while levels of the toxic amyloid-β (Aβ) are higher, indicating a disrupted relationship between these two proteins that may contribute to disease progression.

Skin fibroblasts from Alzheimer's patients also show reduced PKCε levels, suggesting that measuring PKCε in these cells could serve as a non-invasive biomarker for early detection of Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PKCε deficits in Alzheimer's disease brains and skin fibroblasts. Khan, TK., Sen, A., Hongpaisan, J., et al.[2014]

In a 30-week multicenter trial involving 415 patients with mild to moderate Alzheimer's disease, tacrine hydrochloride was found to significantly improve or stabilize cognitive and noncognitive symptoms compared to a placebo, particularly in areas like memory and mood.

The study suggests that tacrine's effects on specific cognitive and noncognitive deficits can be better evaluated by focusing on individual assessment items from the Alzheimer's Disease Assessment Scale (ADAS), enhancing the understanding of its therapeutic impact.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of tacrine on language, praxis, and noncognitive behavioral problems in Alzheimer disease. Raskind, MA., Sadowsky, CH., Sigmund, WR., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04804241

NCT04804241 | Senicapoc in Alzheimer's Disease This pilot study will provide an estimate of treatment effect size on cognitive trajectory, daily function, and brain atrophy. The trial will last 1 year (52 ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6469250/

Repurposing the KCa3.1 inhibitor senicapoc for ... Senicapoc exhibited excellent brain penetrance and oral availability, and in 5xFAD mice, reduced neuroinflammation, decreased cerebral amyloid load, and ...

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04804241/senicapoc-in-alzheimers-disease

Senicapoc in Alzheimer's Disease | Clinical Research Trial ... This pilot study will provide an estimate of treatment effect size on cognitive trajectory, daily function, and brain atrophy. The trial will ...

4. clinicaltrials.eu clinicaltrials.eu/inn/senicapoc/

Senicapoc: A Promising Drug for Various Medical Conditions This article will explore the use of Senicapoc in clinical trials for diseases such as COVID-19, interstitial lung disease, asthma, Alzheimer's disease, and ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0731708521000686

A validated UHPLC-MS/MS method for rapid determination ... Despite a positive outcome in a phase-2 clinical trial [3], senicapoc failed to achieve its primary clinical endpoint in phase-3 trials [4].

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7869607/

A validated UHPLC-MS/MS method for rapid determination of ... Despite a positive outcome in a phase-2 clinical trial [3], senicapoc failed to achieve its primary clinical endpoint in phase-3 trials [4]. However, senicapoc ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5997873/

KCa3.1 Channel Modulators as Potential Therapeutic ... This article will briefly review the available compounds (TRAM-34, senicapoc, NS6180), their binding sites and mechanisms of action.

8. escholarship.org escholarship.org/content/qt1gp96496/qt1gp96496_noSplash_dda4937fa231800c75ed71fd284cec28.pdf?t=p19m9c

KCa3.1 Channel Modulators as Potential Therapeutic ... Since senicapoc had been safe and well ... senicapoc, NS6180 and the 4-phenyl-4H-pyrans to inhibit ... Senicapoc = 2,2-bis-(4-fluorophenyl)-2-phenylacetamide.