Rivastigmine + Scopolamine for Auditory Hallucinations
Recruiting in Palo Alto (17 mi)
Overseen ByAlbert Powers, MD, PhD
Age: 18+
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Yale University
Trial Summary
What is the purpose of this trial?This trial tests two drugs, scopolamine and rivastigmine, on people who hear voices and don't respond to usual treatments. Scopolamine may increase these experiences by affecting how the brain processes information, while rivastigmine may reduce them by improving this process. Rivastigmine has been shown to help with memory and behavior in patients with certain brain disorders. The goal is to find better treatments for these patients.
Will I have to stop taking my current medications?
The trial requires that you stop taking any cholinergic or anticholinergic medications before participating.
What data supports the effectiveness of the drug Rivastigmine for treating auditory hallucinations?
While there is no direct evidence for Rivastigmine's effectiveness in treating auditory hallucinations, studies show that Rivastigmine, especially in patch form, is effective in improving cognitive function in Alzheimer's patients, with fewer side effects compared to capsules. This suggests potential benefits in other cognitive-related conditions.
12345Is the combination of Rivastigmine and Scopolamine safe for humans?
Rivastigmine, used in Alzheimer's treatment, is generally safe and may cause fewer side effects like nausea and vomiting when used as a patch instead of capsules. However, specific safety data for the combination with Scopolamine is not provided in the available research.
12567How is the drug Rivastigmine + Scopolamine unique for treating auditory hallucinations?
Rivastigmine, used in a transdermal patch, provides continuous drug delivery, which may reduce side effects like nausea and vomiting compared to oral capsules. This method of administration is unique as it offers smoother drug levels in the body, potentially improving compliance and effectiveness.
12356Eligibility Criteria
This trial is for English-speaking adults aged 18-65 with a diagnosis of schizophrenia or related disorders, who experience weekly auditory hallucinations. They must be right-handed and not have metal implants, pacemakers, or severe claustrophobia that would prevent MRI scans. Pregnant individuals, those using certain medications, or with a history of substance dependence, significant cognitive impairments, seizures, violence, or specific medical conditions are excluded.Inclusion Criteria
I have been diagnosed with a schizophrenia spectrum disorder.
I speak English.
I am between 18 and 65 years old.
I hear voices at least once a week.
Exclusion Criteria
I have a condition that greatly affects my thinking or memory.
I have had issues with not being able to empty my bladder fully.
I have a history of seizures.
I am currently taking medication that affects my nervous system.
Participant Groups
The study tests if Rivastigmine (a capsule), Scopolamine (a patch), and placebo versions can influence the occurrence of auditory hallucinations in psychosis. It's based on computational models linking brain activity to these symptoms and aims at personalized treatment by pharmacologically altering brain processes involved in hallucinations.
2Treatment groups
Experimental Treatment
Placebo Group
Group I: Aim 2: Those with psychosis/hallucinationsExperimental Treatment2 Interventions
Participants who have a psychosis spectrum diagnosis and frequent auditory hallucinations will be given Rivastigmine capsule versus placebo capsule.
Group II: Aim 1: Healthy ControlsPlacebo Group2 Interventions
Healthy controls will be given scopolamine patches versus placebo patch.
Rivastigmine Capsule is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as Exelon for:
- Alzheimer's disease
- Parkinson's disease dementia
🇪🇺 Approved in European Union as Exelon for:
- Alzheimer's disease
- Parkinson's disease dementia
🇨🇦 Approved in Canada as Exelon for:
- Alzheimer's disease
- Parkinson's disease dementia
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Connecticut Mental Health CenterNew Haven, CT
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Who is running the clinical trial?
Yale UniversityLead Sponsor
National Institute of Mental Health (NIMH)Collaborator
References
Bioavailability Study of a Transdermal Patch Formulation of Rivastigmine Compared with Exelon in Healthy Subjects. [2022]Rivastigmine is a reversible cholinesterase inhibitor indicated for the treatment of all stages of Alzheimer's disease (AD). Transdermal patch formulation allows smooth and continuous drug delivery. Its tolerability, efficacy and convenience of use increase treatment compliance. This study was designed to evaluate the bioavailability and to assess the bioequivalence of two rivastigmine transdermal patches at steady state (RIV-TDS Test Product versus Exelon Marketed Reference Product), with a release rate of 13.3 mg/24 h, after multiple patch applications. As secondary objectives, safety, patch adhesion and skin irritation were evaluated.
Pharmacokinetics and pharmacodynamics of the novel daily rivastigmine transdermal patch compared with twice-daily capsules in Alzheimer's disease patients. [2022]A transdermal patch has been developed for the cholinesterase inhibitor rivastigmine. This study investigated the pharmacokinetics and pharmacodynamics of rivastigmine and NAP226-90, and compared drug exposure between patch and capsule administrations. This was an open-label, parallel-group study in Alzheimer's disease patients randomized to receive either capsule (1.5-6 mg Q12H, i.e., 3-12 mg/day) or patch (5-20 cm2) in ascending doses through four 14-day periods. The patch showed lower Cmax (ca. 30% lower at 20 cm2, 19.5 versus 29.3 ng/ml), longer tmax (8.0 versus 1.0 h), and greater AUC (ca. 1.8-fold at 20 cm2, 345 versus 191 ng x h/ml) compared with the 6 mg Q12H capsule dose, with markedly less fluctuation between peak and trough plasma levels (80% at 20 cm2 versus 620% at 1.5 mg Q12H). Plasma butyrylcholinesterase inhibition rose slowly after patch administration, whereas two distinct peaks were seen after capsule administration. Average exposure with the 10 cm2 patch was comparable to the highest capsule dose (6 mg Q12H, i.e., 12 mg/day).
IDEAL: a 6-month, double-blind, placebo-controlled study of the first skin patch for Alzheimer disease. [2022]The rivastigmine patch is the first transdermal treatment for Alzheimer disease (AD). By providing continuous delivery of drug into the bloodstream over 24 hours, transdermal delivery may offer benefits superior to those of oral administration. This study compared the efficacy, safety and tolerability of rivastigmine patches with capsules and placebo. IDEAL (Investigation of transDermal Exelon in ALzheimer's disease) was a 24-week, double-blind, double-dummy, placebo- and active-controlled study. Patients with AD were randomized to placebo or one of three active treatment target dose groups: 10-cm(2) rivastigmine patch (delivering 9.5 mg/24 hours); 20-cm(2) rivastigmine patch (17.4 mg/24 hours); or 6-mg BID rivastigmine capsules. Primary efficacy measures were the Alzheimer's Disease Assessment Scale-Cognitive subscale and Alzheimer's Disease Cooperative Study-Clinical Global Impression of Change. Secondary outcome measures assessed a range of domains, including behavior, cognitive performance, attention, executive functions, and activities of daily living. A total of 1,195 AD patients participated. All rivastigmine treatment groups showed significant improvement relative to placebo. The 10-cm(2) patch showed similar efficacy to capsules, with approximately two-thirds fewer reports of nausea (7.2% vs 23.1%) and vomiting (6.2% vs 17.0%), incidences statistically not significantly different from placebo (5.0% and 3.3% for nausea and vomiting, respectively). The 20-cm(2) patch showed earlier improvement and numerically superior cognitive scores vs the 10-cm(2) patch with similar tolerability to capsules. Local skin tolerability was good. The transdermal patch with rivastigmine may offer additional therapeutic benefits and may prove to be the best delivery system for this drug to treat AD.
From high doses of oral rivastigmine to transdermal rivastigmine patches: user experience and satisfaction among caregivers of patients with mild to moderate Alzheimer disease. [2015]Rivastigmine, a treatment for mild to moderate Alzheimer disease (AD), is the first cholinesterase inhibitor to be available in the transdermal format. We aim to describe user experience and satisfaction with the rivastigmine patch, as well as any clinical changes perceived in patients.
Pharmacokinetic rationale for the rivastigmine patch. [2019]The dual cholinesterase inhibitor rivastigmine is approved in capsule form in many countries for the symptomatic treatment of dementia associated with Alzheimer disease (AD) and Parkinson disease (PD). All orally administered cholinesterase inhibitors are associated with central cholinergic gastrointestinal side effects, particularly during the titration phase, which are believed to be caused by a rapid increase in brain acetylcholine levels after effective inhibition of the target enzymes. A recently developed rivastigmine transdermal patch may have the potential to reduce such side effects. Pharmacokinetic studies have shown that transdermal administration of rivastigmine prolongs t(max), lowers C(max), and reduces fluctuations in plasma concentration. The 10-cm(2) rivastigmine patch provides comparable exposure (area under the curve, AUC) to the highest capsule dose (6-mg BID) and may be the target maintenance dose for most patients, delivering optimal rivastigmine exposure to produce a therapeutic effect. The potential of a patch to improve the tolerability of rivastigmine (e.g., nausea and vomiting) while permitting similar exposure to the highest doses of capsules may, in turn, lead to improved efficacy and compliance.
Bioequivalence Study of Rivastigmine 6 mg Capsules (Single Dose) in Healthy Volunteers. [2018]To assess the bioequivalence of generic formulation of rivastigmine (test) and Exelon (reference).
Efficacy and safety of switching from oral cholinesterase inhibitors to the rivastigmine transdermal patch in patients with probable Alzheimer's disease. [2022]The goal of this study was to estimate the efficacy and safety of the rivastigmine transdermal patch in patients with probable Alzheimer's disease (AD) who cannot tolerate or do not respond to oral cholinesterase inhibitors (ChEIs).