Senicapoc for Alzheimer's Disease
(Senicapoc Trial)
Recruiting in Palo Alto (17 mi)
+1 other location
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.
12345Eligibility 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.
+6 more
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.
+18 more
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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: 10 mg daily SenicapocExperimental Treatment1 Intervention
10 mg daily Senicapoc for 52 weeks
Group II: Placebo GroupPlacebo Group1 Intervention
Placebo daily for 52 weeks
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of California, Davis Alzheimer's Disease CenterSacramento, CA
UC Davis Alzheimer's Disease Center East BayWalnut Creek, CA
Loading ...
Who Is Running the Clinical Trial?
University of California, DavisLead Sponsor
References
Benzolactam (BL) enhances sAPP secretion in fibroblasts and in PC12 cells. [2019]Activation of protein kinase C is known to favor the alpha-secretase processing of the Alzheimer's disease (AD) amyloid precursor protein (APP), resulting in the generation of non-amyloidogenic soluble APP (sAPP). Consequently, the relative secretion of amyloidogenic Abeta1-40 and Abeta1-42(3) is reduced. This is particularly relevant since fibroblasts and other cells expressing APP and presenilin AD mutations secrete increased amounts of total Abeta and/or increased ratios of Abeta1-42(3)/Abeta1-40. Interestingly, PKC defects have been found in AD brain alpha and beta isoforms) and in fibroblasts (alpha isoform) from AD patients. Here, we use a novel PKC activator (benzolactam, BL) with improved selectivity for the alpha, beta and gamma isoforms to enhance sAPP secretion in fibroblasts from AD patients and in PC12 cells. Incubation (2 h) of AD fibroblasts with BL (1 and 10 microM) resulted in significant increases of sAPP secretion over basal levels. sAPP secretion in BL-treated AD cells was also slightly higher compared to control BL-treated fibroblasts, which only showed significant increases of sAPP secretion after treatment with 10 microM BL. Staurosporine (a PKC inhibitor) eliminated the effects of BL in both control and AD fibroblasts. BL and a related compound (LQ12) also caused an approximately 3-fold sAPP secretion in PC12 cells. The use of a novel and possibly non-tumorigenic PKC activator may prove useful to favor non-amyloidogenic APP processing and is, therefore, of potential therapeutic value.
Efficacy and safety of tarenflurbil in mild to moderate Alzheimer's disease: a randomised phase II trial. [2016]The amyloid-beta peptide Abeta(42) has been implicated in the pathogenesis of Alzheimer's disease (AD). We aimed to test the effects of tarenflurbil, a selective Abeta(42)-lowering agent (SALA), on cognition and function in patients with mild to moderate AD.
Trials to slow progression and prevent disease onset. [2019]Current treatments for Alzheimer's disease (AD) are largely symptomatic and improve cognition. Only a single trial of selegiline and vitamin E has been demonstrated to delay progression of the time to clinically important endpoints in this disease. Effective treatments currently under development are designed to either slow the rate of progression or delay the time of onset. Classes of agents currently being investigated include: antioxidants, anti-inflammatory agents, growth factors, hormones, and drugs designed to prevent the deposition or enhance the removal of amyloid. In addition to trials designed to slow the rate of progression, several primary prevention trials have already been initiated. Finally, a series of trials designed to prevent the development of AD in patients with mild cognitive impairment have been initiated.
Effect of tacrine on language, praxis, and noncognitive behavioral problems in Alzheimer disease. [2019]To examine the effects of tacrine hydrochloride in patients with Alzheimer disease (AD) and detectable baseline deficits in discrete cognitive and noncognitive parameters who are enrolled in a previously reported multicenter, double-blind, 30-week trial.
PKCε deficits in Alzheimer's disease brains and skin fibroblasts. [2014]In Alzheimer's disease (AD) transgenic mice, activation of synaptogenic protein kinase C ε (PKCε) was found to prevent synaptotoxic amyloid-β (Aβ)-oligomer elevation, PKCε deficits, early synaptic loss, cognitive deficits, and amyloid plaque formation. In humans, to study the role of PKCε in the pathophysiology of AD and to evaluate its possible use as an early AD-biomarker, we examined PKCε and Aβ in the brains of autopsy-confirmed AD patients (n = 20) and age-matched controls (AC, n = 19), and in skin fibroblast samples from AD (n = 14), non-AD dementia patients (n = 14), and AC (n = 22). Intraneuronal Aβ levels were measured immunohistochemically (using an Aβ-specific antibody) in hippocampal pyramidal cells of human autopsy brains. PKCε was significantly lower in the hippocampus and temporal pole areas of AD brains, whereas Aβ levels were significantly higher. The ratio of PKCε to Aβ in individual CA1 pyramidal cells was markedly lower in the autopsy AD brains versus controls. PKCε was inversely correlated with Aβ levels in controls, whereas in AD patients, PKCε showed no significant correlation with Aβ. In autopsy brains, PKCε decreased as the Braak score increased. Skin fibroblast samples from AD patients also demonstrated a deficit in PKCε compared to controls and an AD-specific change in the Aβ-oligomer effects on PKCε. Together, these data demonstrate that the relationship between Aβ levels and PKCε is markedly altered in AD patients' brains and skin fibroblasts, reflecting a loss of protective effect of PKCε against toxic Aβ accumulation. These changes of PKCε levels in human skin fibroblasts may provide an accurate, non-invasive peripheral AD biomarker.