Senicapoc for Alzheimer's Disease

(Senicapoc Trial)

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen by John Olichney, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Trial Summary

What is the purpose of this trial?

This trial tests Senicapoc, a drug that may reduce brain inflammation, in patients with early-stage Alzheimer's disease. The goal is to see if it can slow down memory loss and other symptoms by protecting brain cells.

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.

How is the drug Senicapoc unique in treating Alzheimer's disease?

Senicapoc is unique because it may work by targeting protein kinase C (PKC), which is involved in processing proteins related to Alzheimer's disease. This approach is different from most current treatments that focus on improving symptoms rather than altering the disease process itself. ^{1 2 3 4 5}

Research Team

John Olichney, MD

Principal Investigator

University of California, Davis

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Senicapoc (Ion Channel Blocker)

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.

Participant Groups

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+

Rakesh Dixit

University of California, Davis

Chief Executive Officer since 2024

PhD in Biochemistry and Molecular Biology from the University of California, Davis

Suresh Mahabhashyam

University of California, Davis

Chief Medical Officer since 2020

MD from Bangalore Medical College

Findings from Research

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]

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]

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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

Benzolactam (BL) enhances sAPP secretion in fibroblasts and in PC12 cells. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Efficacy and safety of tarenflurbil in mild to moderate Alzheimer's disease: a randomised phase II trial. [2016]

3. Austria pubmed.ncbi.nlm.nih.gov

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

4. United States pubmed.ncbi.nlm.nih.gov

Effect of tacrine on language, praxis, and noncognitive behavioral problems in Alzheimer disease. [2019]

5. Netherlands pubmed.ncbi.nlm.nih.gov

PKCε deficits in Alzheimer's disease brains and skin fibroblasts. [2014]