Rivastigmine + Scopolamine for Auditory Hallucinations

Recruiting in Palo Alto (17 mi)

Overseen by Albert Powers, MD, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase < 1

Recruiting

Sponsor: Yale University

Must be taking: Dopamine-2 antagonists

Must not be taking: Cholinergics, Anticholinergics

Disqualifiers: Substance dependence, Neurological problems, Pregnancy, others

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. ^{1 2 3 4 5}

Is 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. ^{1 2 5 6 7}

How 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. ^{1 2 3 5 6}

Research Team

Albert Powers, MD, PhD

Principal Investigator

Yale University

Eligibility 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

You are right-handed.

I speak English.

I am between 18 and 65 years old.

Exclusion Criteria

You have a history of being physically aggressive or violent.

I have a history of seizures.

There are signs of heart problems on an EKG test.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive scopolamine or rivastigmine to assess effects on conditioned hallucinations and prior weighting

6 weeks

Weekly visits for drug administration and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Physostigmine Salicylate (Drug)
• Placebo (Drug)
• Placebo Capsule (Drug)
• Placebo Patch (Drug)
• Rivastigmine Capsule (Cholinesterase Inhibitor)
• Rivastigmine Transdermal Product (Cholinesterase Inhibitor)
• Saline (Drug)
• Scopolamine (Drug)

Trial Overview 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.

Participant Groups

Group I: Aim 2: Those with psychosis/hallucinations Experimental Treatment 2 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 Controls Placebo Group 2 Interventions

Healthy controls will be given scopolamine patches versus placebo patch.

Rivastigmine Capsule is already approved in Canada for the following indications:

Approved in Canada as Exelon for:

• Alzheimer's disease
• Parkinson's disease dementia

Who Is Running the Clinical Trial?

Yale University

Lead Sponsor

Trials

1,963

Recruited

3,046,000+

Nancy J. Brown

Yale University

Chief Medical Officer since 2020

MD from Yale School of Medicine

Peter Salovey

Yale University

Chief Executive Officer since 2013

PhD in Psychology from Yale University

National Institute of Mental Health (NIMH)

Collaborator

Trials

3,007

Recruited

2,852,000+

Dr. Joshua A. Gordon

National Institute of Mental Health (NIMH)

Chief Executive Officer since 2016

MD, PhD

Dr. Shelli Avenevoli

National Institute of Mental Health (NIMH)

Chief Medical Officer

PhD

Findings from Research

The study demonstrated that the new rivastigmine transdermal patch (RIV-TDS) is bioequivalent to the marketed Exelon patch, meaning they deliver the same amount of the drug into the bloodstream, which is important for consistent treatment of Alzheimer's disease.

RIV-TDS showed better skin adhesion and tolerability compared to the reference product, suggesting it may enhance patient compliance and comfort during treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioavailability Study of a Transdermal Patch Formulation of Rivastigmine Compared with Exelon in Healthy Subjects. Morte, A., Vaqué, A., Iniesta, M., et al.[2022]

The transdermal patch for rivastigmine provides a more stable drug exposure compared to the oral capsule, with lower peak levels and less fluctuation in plasma concentrations, which may enhance safety and tolerability for patients with Alzheimer's disease.

In this study involving Alzheimer's patients, the patch demonstrated comparable efficacy to the highest oral dose while allowing for a more gradual increase in drug levels, potentially leading to improved therapeutic outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetics and pharmacodynamics of the novel daily rivastigmine transdermal patch compared with twice-daily capsules in Alzheimer's disease patients. Lefèvre, G., Sedek, G., Jhee, SS., et al.[2022]

The rivastigmine patch, a transdermal treatment for Alzheimer's disease, demonstrated significant cognitive improvements in 1,195 patients over 24 weeks compared to placebo, with the 10-cm² patch showing similar efficacy to oral capsules but with fewer side effects like nausea and vomiting.

The 20-cm² patch provided earlier cognitive improvements and better scores than the 10-cm² patch, while maintaining good tolerability, suggesting that transdermal delivery may be a superior method for administering rivastigmine in treating Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IDEAL: a 6-month, double-blind, placebo-controlled study of the first skin patch for Alzheimer disease. Winblad, B., Grossberg, G., Frölich, L., et al.[2022]

In a study involving 1851 caregivers of patients with mild to moderate Alzheimer's disease, 94.3% preferred the transdermal rivastigmine patch over oral treatment, highlighting its user-friendly format.

Caregivers reported high satisfaction (76.5%) with the patch, noting it was easy to apply and had minimal impact on daily activities, while also observing clinical improvements in patients compared to previous oral treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

From high doses of oral rivastigmine to transdermal rivastigmine patches: user experience and satisfaction among caregivers of patients with mild to moderate Alzheimer disease. Reñé, R., Ricart, J., Hernández, B.[2015]

The rivastigmine transdermal patch offers a promising alternative to oral capsules for treating dementia, potentially reducing gastrointestinal side effects like nausea and vomiting that are common with oral cholinesterase inhibitors.

Pharmacokinetic studies indicate that the patch provides similar drug exposure to the highest oral dose while minimizing fluctuations in plasma concentration, which may enhance tolerability and improve patient compliance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmacokinetic rationale for the rivastigmine patch. Cummings, J., Lefèvre, G., Small, G., et al.[2019]

A study involving 40 healthy men demonstrated that the generic formulation of rivastigmine is bioequivalent to the brand Exelon, with similar pharmacokinetic profiles as shown by comparable AUC and Cmax values.

Both the generic and reference formulations were well tolerated by participants, indicating that the generic version is a safe alternative to the brand-name drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioequivalence Study of Rivastigmine 6 mg Capsules (Single Dose) in Healthy Volunteers. Abhyankar, D., Shedage, A., Gole, M., et al.[2018]

References

1. France pubmed.ncbi.nlm.nih.gov

Bioavailability Study of a Transdermal Patch Formulation of Rivastigmine Compared with Exelon in Healthy Subjects. [2022]

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

Pharmacokinetics and pharmacodynamics of the novel daily rivastigmine transdermal patch compared with twice-daily capsules in Alzheimer's disease patients. [2022]

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

IDEAL: a 6-month, double-blind, placebo-controlled study of the first skin patch for Alzheimer disease. [2022]

4. Spain pubmed.ncbi.nlm.nih.gov

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]

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

Pharmacokinetic rationale for the rivastigmine patch. [2019]

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

Bioequivalence Study of Rivastigmine 6 mg Capsules (Single Dose) in Healthy Volunteers. [2018]

7. Korea (South) pubmed.ncbi.nlm.nih.gov

Efficacy and safety of switching from oral cholinesterase inhibitors to the rivastigmine transdermal patch in patients with probable Alzheimer's disease. [2022]