Mecamylamine Challenge for Cognitive Impairment

(AMoCC-SCD Trial)

Overseen By Kimberly Albert, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Vanderbilt University Medical Center

Disqualifiers: Stroke, Epilepsy, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 3

Duration: 1 week

80 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how the drug mecamylamine affects attention in older adults concerned about memory problems. Researchers believe that some people maintain sharp cognitive skills by using extra brain power, but mecamylamine may disrupt this by affecting brain chemicals linked to attention. Participants will receive either mecamylamine or a placebo (a harmless pill) to assess its impact on attention. This trial may suit individuals aged 55 or older, who do not smoke, and who are concerned about their cognitive abilities without having major neurological conditions. As an Early Phase 1 trial, this research focuses on understanding how mecamylamine works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that mecamylamine can impact thinking and attention. Some studies found that people taking mecamylamine might experience slower reaction times or make more mistakes on tests assessing learning and focus. Higher doses could intensify these effects. Mecamylamine affects brain areas that use acetylcholine, a chemical important for attention and learning. Despite these effects, the treatment is generally tolerated for short-term use. However, this study is in its early stages, so information on safety for this specific use is limited. Participants should consult the study team to understand potential risks and benefits. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about mecamylamine for cognitive impairment because it offers a fresh approach compared to existing treatments, which often focus on enhancing neurotransmitter activity. Mecamylamine uniquely works as an anticholinergic agent, blocking specific receptors in the brain, which might help manage cognitive symptoms differently. This novel mechanism could provide an alternative for patients who don't respond well to current options, potentially offering quicker or more effective relief.

What evidence suggests that mecamylamine might be an effective treatment for cognitive impairment?

Research shows that mecamylamine can impact thinking skills, temporarily reducing abilities like attention and memory. One study found that taking mecamylamine caused noticeable problems with focusing and tasks involving hand-eye coordination. Another study discovered that even a very small dose could improve memory for recognizing things, highlighting its complex effects on the brain. In this trial, participants will receive either mecamylamine or a placebo to study its effects on cognitive issues. These findings suggest that mecamylamine can change attention and thinking abilities, prompting its study in this trial. ^{1 6 7 8 9}

Who Is on the Research Team?

Paul Newhouse, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for non-smokers aged 55 or older who feel their memory isn't as good as it used to be but can still score above 25 on a cognitive test (MoCA) and have mild concerns about their memory without serious impairment. People with medical issues that make the drug risky, or major brain conditions like stroke or epilepsy cannot join.

Inclusion Criteria

I am 55 years old or older.

Montreal Cognitive Assessment (MoCA) score must be greater than 25 AND Global Deterioration Scale (GDS) rating must be less than 3

Must be non-smokers

Exclusion Criteria

I cannot take certain medications due to health risks.

I have a history of a major brain disorder like stroke or epilepsy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants undergo two study visits with double-blinded administration of mecamylamine or placebo, including cognitive testing and EEG sessions

1 week

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

What Are the Treatments Tested in This Trial?

Interventions

• Mecamylamine
• Placebo Comparator Challenge

Trial Overview The study is testing how an anticholinergic drug called Mecamylamine affects attention in people with slight memory concerns by comparing it to a placebo. Researchers will use EEGs to look at brain activity and tests of attention to see if the drug changes how well participants can focus.

How Is the Trial Designed?

Group I: Anticholinergic Challenge Experimental Treatment 1 Intervention

All participants will receive oral mecamylamine for 1 day

Group II: Placebo Challenge Placebo Group 1 Intervention

All participants will receive oral placebo for 1 day

Mecamylamine is already approved in United States, Canada for the following indications:

Approved in United States as Inversine for:

• Hypertension
• Nicotine dependence

Approved in Canada as Inversine for:

• Hypertension

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Published Research Related to This Trial

Memantine is a groundbreaking medication for moderate to severe Alzheimer's disease, acting as a moderate-affinity, uncompetitive NMDA receptor antagonist that helps to regulate glutamate activity in the brain.

Since its FDA approval in 2003, memantine has been shown to improve cognitive function, reduce behavioral issues, enhance daily living activities, and delay the need for institutional care in patients, especially when used alongside donepezil.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Classics in Chemical Neuroscience: Memantine. Alam, S., Lingenfelter, KS., Bender, AM., et al.[2022]

In a study involving 60 adults aged 50-79, memantine was found to improve attention and information processing speed in individuals with Age-Associated Memory Impairment (AAMI) over a 90-day treatment period.

The treatment was well-tolerated, with no significant differences in adverse events between those taking memantine and those on a placebo, indicating its safety for this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, placebo-controlled trial of memantine in age-associated memory impairment (memantine in AAMI). Ferris, S., Schneider, L., Farmer, M., et al.[2013]

In a double-blind, randomized, placebo-controlled trial involving subjects with multiple sclerosis and cognitive impairment, memantine did not show any significant improvement in cognitive performance compared to placebo, as measured by the PASAT and CVLT-II tests.

While memantine was generally safe with no serious adverse events reported, it was associated with increased fatigue and neurological side effects, and family members reported less cognitive improvement and more neuropsychiatric symptoms in those taking memantine compared to those on placebo.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine for cognitive impairment in multiple sclerosis: a randomized placebo-controlled trial. Lovera, JF., Frohman, E., Brown, TR., et al.[2021]

A six-month study involving 50 patients with mild to moderate Alzheimer's disease found that both original memantine and the generic version (memantal) showed similar efficacy in improving cognitive functions and neuropsychiatric symptoms.

There were no significant differences in safety or effectiveness between the two medications, indicating that the generic memantal is a viable alternative to the original memantine for treating dementia in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[A comparison of the efficacy and safety of memantal and original memantine in the treatment of mild and moderate dementia in Alzheimer's disease]. Shiryaev, OY., Shapovalov, DL., Polozova, TM., et al.[2018]

Memantine, used for treating moderate to severe Alzheimer's disease, has been shown to have a favorable safety and tolerability profile, with adverse events similar in frequency to those experienced by patients on placebo, based on data from 2311 patients in six trials lasting at least 24 weeks.

The analysis indicates that both short- and long-term treatment with memantine is safe, with minimal adverse effects, and discontinuation rates due to side effects were comparable between memantine and placebo groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Memantine for the treatment of Alzheimer's disease: tolerability and safety data from clinical trials. Farlow, MR., Graham, SM., Alva, G.[2021]

Mecamylamine, originally used as an antihypertensive agent, is now being explored for its effectiveness at much lower doses (2.5 - 10 mg) in blocking nicotine's effects and treating neuropsychiatric disorders due to its ability to cross the blood-brain barrier.

Recent Phase II clinical trials have shown that mecamylamine may have antidepressant effects and could serve as an augmentation therapy for patients with major depression who do not respond to standard SSRI treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mecamylamine - a nicotinic acetylcholine receptor antagonist with potential for the treatment of neuropsychiatric disorders. Bacher, I., Wu, B., Shytle, DR., et al.[2013]

A review of cardiovascular adverse drug reactions (ADRs) associated with memantine identified 36 cases, including 18 reports of bradycardia, indicating a potential link between memantine and heart-related side effects.

Most cases of bradycardia resolved after discontinuing memantine, suggesting that while memantine may cause cardiac ADRs, the exact mechanism behind these effects is still not well understood.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does memantine induce bradycardia? A study in the French PharmacoVigilance Database. Gallini, A., Sommet, A., Montastruc, JL.[2013]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5903244/

Reversal of mecamylamine‐induced effects in healthy ... Mecamylamine 30 mg induced significant disturbances of cognitive functions. Attention and execution of visual (fine) motor tasks was decreased, short‐ and long‐ ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2776071/

Effects of acute ultra-low dose mecamylamine on cognition ... Results. The 0.5 mg dose of mecamylamine significantly improved recognition memory and reduced tolerance for delay. Mecamylamine increased participant rated ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/0091305789904942

Reversal of a mecamylamine-induced cognitive deficit with ... In the current study, the D2 agonist LY 171555 was found to be effective in reversing the radial-arm maze choice accuracy impairment caused by mecamylamine.

4. withpower.com withpower.com/trial/early-phase-1-cognitive-dysfunction-8-2023-0a6f4

Mecamylamine Challenge for Cognitive Impairment Trial Overview The study is testing how an anticholinergic drug called Mecamylamine affects attention in people with slight memory concerns by comparing it to a ...

5. bpspubs.onlinelibrary.wiley.com bpspubs.onlinelibrary.wiley.com/doi/10.1111/bcp.13268

An anti‐nicotinic cognitive challenge model using ... This study demonstrated that mecamylamine causes nicotinic receptor specific temporary decline in cognitive functioning. Compared with the ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5510063/

An anti‐nicotinic cognitive challenge model using ... This study aims to characterize a nicotinic anticholinergic challenge model using mecamylamine and to compare it to the scopolamine model.

7. nature.com nature.com/articles/npp199411.pdf

Age-Related Effects of the Nicotinic Antagonist ... We have presented preliminary data suggesting that mecamylamine administered acutely to young healthy males produces impairment of several cognitive.

8. sciencedirect.com sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/mecamylamine

Mecamylamine - an overview Furthermore, high doses of mecamylamine may produce cognitive deficits. Since mecamylamine interacts nonselectively with all known nAChR subtypes, the ...

9. researchgate.net researchgate.net/publication/11984170_Mecamylamine_New_therapeutic_uses_and_toxicityrisk_profile

Mecamylamine: New therapeutic uses and toxicity/risk profile This review describes nonclinical and clinical data pertaining to the pharmacology, toxicity, and tolerability of mecamylamine, including some ...