Neostigmine + Glycopyrrolate for Neurogenic Bowel

No longer recruiting at 1 trial location

Overseen By Mark Korsten, MD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: James J. Peters Veterans Affairs Medical Center

Must not be taking: Cholinesterase inhibitors, Antidepressants

Disqualifiers: Hypertension, Heart disease, Pregnancy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 1 week

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to help individuals with spinal cord injuries manage bowel problems more easily. Researchers are testing a combination of two medications delivered through the skin using a painless electrical current via a novel wireless iontophoresis device. This approach could simplify home management of the condition, eliminating the need for injections. Individuals with spinal cord injuries who experience bowel issues may be suitable for this trial, provided they do not have certain health conditions like heart problems or allergies to specific substances. As an Early Phase 1 trial, the research aims to understand how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative approach.

Do I have to stop taking my current medications for the trial?

Yes, you may need to stop taking certain medications. The trial excludes participants currently treated with cholinesterase inhibitors or anti-depressants, and those taking medications that could result in adverse reactions with neostigmine and/or glycopyrrolate. A study physician will determine if your medications are compatible.

What prior data suggests that this wireless iontophoresis device is safe for transdermal administration?

Research has shown that a combination of two medicines, neostigmine and glycopyrrolate, can be safely administered through the skin using iontophoresis. This technique employs a gentle electrical current to deliver the medicine without needles. Studies have found that this method is not only safe but also aids people with spinal cord injuries in achieving regular bowel movements. No major safety issues have been reported, and patients have generally tolerated the treatment well. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using Neostigmine and Glycopyrrolate for neurogenic bowel because this treatment is delivered through a novel wireless iontophoresis device, offering a non-invasive and potentially more convenient alternative to traditional oral or injectable medications. Unlike standard treatments, which often involve oral laxatives or enemas, this method uses a transdermal approach that could improve patient compliance and reduce side effects. Additionally, the use of iontophoresis allows for controlled drug delivery, potentially enhancing the efficacy of the treatment by ensuring a steady release of medication directly through the skin.

What evidence suggests that this wireless iontophoresis device is effective for neurogenic bowel?

Research has shown that using neostigmine and glycopyrrolate together can safely aid bowel movements in people with spinal cord injuries. In this trial, participants will receive these medications transdermally via a novel wireless iontophoresis device. Studies have found that applying these drugs through the skin with a mild electrical current (iontophoresis) can expedite bowel movements. This needle-free method appears to have fewer side effects than other treatments. Overall, this approach seems promising for helping those with spinal cord injuries manage bowel issues more easily. ^{1 2 3 4 5}

Who Is on the Research Team?

Christopher P Cardozo, M.D.

Principal Investigator

James J. Peters Veterans Affairs Medical Center

Are You a Good Fit for This Trial?

This trial is for individuals with spinal cord injury who experience neurogenic bowel disorders, including bowel incontinence and constipation. Participants should be those seeking a non-invasive method to induce bowel evacuation.

Inclusion Criteria

I am physically capable.

I am either male or female.

Exclusion Criteria

Lactating, nursing females

Previous adverse reaction or hypersensitivity to electrical stimulation

Known sensitivity (prior reaction or allergy) to neostigmine or glycopyrrolate

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Treatment

Participants receive transdermal administration of vitamin B12, neostigmine, and glycopyrrolate using wireless and wired ION devices over three consecutive days

1 week

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including recording of heart rate, bowel sounds, blood pressure, and adverse symptoms

1 week

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Transdermal Administration by a Novel Wireless Iontophoresis Device

Trial Overview The study tests a wireless iontophoresis device called I-Box by Dynatronics, which delivers a combination of drugs (Neostigmine and Glycopyrrolate) through the skin using electrical current to promote bowel movement without needles.

How Is the Trial Designed?

Group I: Primary Experimental Treatment 2 Interventions

6 subjects will receive 2 medications transdermally.

Transdermal Administration by a Novel Wireless Iontophoresis Device is already approved in United States for the following indications:

Approved in United States as Wireless Iontophoresis Device for:

• Neurogenic bowel disorders in persons with spinal cord injury

Who Is Running the Clinical Trial?

James J. Peters Veterans Affairs Medical Center

Lead Sponsor

Trials

59

Recruited

2,900+

Published Research Related to This Trial

The iontophoresis-driven porous microneedle array patch (IDPMAP) allows for highly effective transdermal delivery of charged macromolecular drugs, achieving a 99% skin penetration rate with minimal side effects like irritation or hypersensitivity.

In vivo studies in type 1 diabetic rats showed that IDPMAP effectively delivered insulin nanovesicles, maintaining normal blood glucose levels for about 5.4 hours, demonstrating superior control and efficiency compared to traditional methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iontophoresis-driven porous microneedle array patch for active transdermal drug delivery. Li, Y., Yang, J., Zheng, Y., et al.[2021]

ARN14140, a conjugate designed to target both cholinergic and glutamatergic pathways for Alzheimer's treatment, can be effectively delivered through transdermal iontophoresis, achieving a high delivery efficiency of 76.9%.

In vivo studies in male Wistar rats confirmed that this noninvasive method allows for controlled delivery of ARN14140 to both the blood and brain, marking a significant advancement in drug administration for Alzheimer's disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled Iontophoretic Delivery in Vitro and in Vivo of ARN14140-A Multitarget Compound for Alzheimer's Disease. Singhal, M., Merino, V., Rosini, M., et al.[2020]

The study demonstrated that transdermal iontophoretic delivery of tacrine hydrochloride in Sprague Dawley rats is feasible, with plasma concentration profiles showing a dependency on both current strength and drug concentration, indicating effective absorption.

In vivo results correlated with in vitro permeation studies, suggesting that tacrine can reach therapeutic levels through this delivery method, although in vitro permeation rates were higher than in vivo absorption rates, highlighting the need for further optimization.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transdermal iontophoretic delivery of tacrine hydrochloride: Correlation between in vitro permeation and in vivo performance in rats. Patel, N., Jain, S., Lin, S.[2017]

Transdermal iontophoretic drug delivery has been limited to short-term applications due to side effects like skin trauma caused by high current density, but new techniques can help reduce these effects.

By optimizing drug formulations and controlling factors like pH and skin permselectivity, it is possible to achieve effective drug delivery with lower current, minimizing side effects while maintaining therapeutic efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iontophoretic delivery of nonpeptide drugs: formulation optimization for maximum skin permeability. Sanderson, JE., de Riel, S., Dixon, R.[2019]

Water-soluble polypyrrole nanoparticles (WS-PPyNPs) significantly enhance the transdermal delivery of insulin (INS) through iontophoresis, achieving a cumulative drug permeation of 68.29 µg cm-2 with cathodal stimulation, compared to only 20.48 µg cm-2 with anodal stimulation.

The study demonstrates that WS-PPyNPs can effectively replace doped dodecyl sulfate with insulin, improving drug delivery compared to passive methods, indicating their potential for controlled transdermal insulin therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled Transdermal Iontophoresis of Insulin from Water-Soluble Polypyrrole Nanoparticles: An In Vitro Study. Tari, K., Khamoushian, S., Madrakian, T., et al.[2021]

The study optimized the transdermal delivery of thyrotropin-releasing hormone (TRH) using iontophoresis, achieving a maximum delivery rate of 103.2 micrograms per hour per square centimeter under specific conditions (pH 7.0, ionic strength 0.037, and a 75% duty cycle).

The delivery rate of TRH could vary significantly (two to ten-fold) based on the operational parameters, highlighting the importance of optimizing these conditions for effective transdermal drug delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Response surface method: a novel strategy to optimize iontophoretic transdermal delivery of thyrotropin-releasing hormone. Huang, YY., Wu, SM., Wang, CY.[2019]

Memantine, a treatment for moderate to severe Alzheimer's disease, can be effectively delivered through transdermal therapeutic systems (TTS), which may improve patient compliance compared to oral administration.

The study found that iontophoretic delivery of memantine achieved significantly higher skin transport rates (46.4 μg/cm²/h) compared to passive delivery (8.89 μg/cm²/h), suggesting that this method could provide effective therapeutic levels of the drug.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transdermal therapeutic systems for memantine delivery. Comparison of passive and iontophoretic transport. Del Río-Sancho, S., Serna-Jiménez, CE., Sebastián-Morelló, M., et al.[2017]

In a study involving 31 participants with patellar tendinopathy, both the wireless iontophoresis patch and the wired dose controller showed similar effectiveness in reducing pain during functional tasks, specifically the sit-to-stand test.

All treatment groups, including the sham group, reported improvements in knee pain, indicating a possible placebo effect; however, the active treatments were more effective in reducing pain during specific activities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Wireless Versus Wired Iontophoresis for Treating Patellar Tendinopathy: A Randomized Clinical Trial. Rigby, JH., Mortensen, BB., Draper, DO.[2018]

Transdermal iontophoretic delivery of apomorphine in patients with Parkinson's disease can be effectively controlled by the applied electrical current, leading to significant increases in drug transport rates.

Optimizing conditions such as temperature and donor concentration can achieve transport rates that may reach therapeutically effective plasma concentrations, suggesting potential for effective treatment delivery through the skin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Iontophoretic delivery of apomorphine. I: In vitro optimization and validation. van der Geest, R., Danhof, M., Boddé, HE.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06351995

Neostigmine and Glycopyrrolate by Iontophoresis | ... NEO and GLY can be delivered into the systemic circulation by transcutaneous route by ION to induce a safe and predictable bowel evacuation in persons with SCI.

2. mdpi.com mdpi.com/2077-0383/10/5/1135

The Addition of Transdermal Delivery of Neostigmine and ... The transdermal delivery of neostigmine and glycopyrrolate by iontophoresis substantially reduced the time to bowel evacuation in patients undergoing routine ...

3. apps.dtic.mil apps.dtic.mil/sti/trecms/pdf/AD1119068.pdf

Neostigmine and Glycopyrrolate by Iontophoresis to Induce ... The primary objective is to determine a lower effective dose to induce BE by transcutaneous administration of NEO by ION. 2. KEYWORDS: Provide a brief list of ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT06351852

Transdermal Administration by a Novel Wireless ... To address this problem, a dual medication combination (neostigmine and glycopyrrolate) was developed that safely and predictably caused the bowel to empty ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5839930/

Delivery of Neostigmine and Glycopyrrolate by Iontophoresis Another 5 individuals had a bowel movement after high-dose transdermal neostigmine/glycopyrrolate administration. Fewer side effects were ...