Neostigmine + Glycopyrrolate for Constipation

Not currently recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: James J. Peters Veterans Affairs Medical Center

Must not be taking: Cholinesterase inhibitors, Anticholinergics

Disqualifiers: Hypertension, Heart disease, Pregnancy, others

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

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 2

Duration: 2 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method to treat constipation using two medications, neostigmine (also known as Prostigmin, Bloxiverz, or neostigmine methylsulfate) and glycopyrrolate, delivered through the skin with a special technique. Researchers aim to determine the lowest effective dose to ease bowel movements. This treatment may suit adults who have had a spinal cord injury for over a year and struggle with constipation, including pain, straining, or accidents. As a Phase 3 trial, this treatment is in the final step before FDA approval, offering participants a chance to contribute to a potentially groundbreaking therapy.

Do I need to stop my current medications for the trial?

Yes, you may need to stop certain medications. The trial excludes participants currently taking specific medications that could interact with neostigmine or glycopyrrolate, such as certain antidepressants and medications for Parkinson's Disease or dementia. It's best to discuss your current medications with the study physician to see if they are allowed.

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

Research has shown that neostigmine combined with glycopyrrolate impacts bowel movements. Neostigmine can significantly aid bowel movements, particularly in individuals with chronic constipation, though it may also cause bradycardia, or a slower heart rate.

Clear safety information about using this combination during pregnancy is lacking, but it effectively promotes bowel movement, which is the treatment's goal.

Generally, neostigmine and glycopyrrolate are well-tolerated, though some individuals might experience changes in heart rate. Participants should discuss any concerns with their healthcare provider.

Overall, despite some known side effects, studies suggest this combination may be a promising option for treating constipation under medical supervision. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Most treatments for constipation work by softening the stool or stimulating bowel movements, often taking the form of over-the-counter laxatives or fiber supplements. However, the combination of Neostigmine and Glycopyrrolate offers a fresh approach by directly targeting the nerves that stimulate bowel movement, which is quite different from traditional methods. This treatment is unique because it is administered intravenously and through a specialized ION system, potentially leading to more controlled and immediate effects. Researchers are excited about this innovative delivery method as it might offer faster relief for constipation compared to existing treatments.

What evidence suggests that neostigmine and glycopyrrolate might be effective for constipation?

Research has shown that using neostigmine and glycopyrrolate together can aid bowel movements. In this trial, participants will receive this combination to assess its effectiveness in relieving constipation. Neostigmine improves gut muscle function, facilitating stool movement through the intestines. Glycopyrrolate reduces some side effects of neostigmine, enhancing treatment comfort. Together, they have effectively relieved constipation, even in challenging cases like pseudo-obstruction, where the intestine behaves as if blocked. These findings suggest that this combination could be a promising treatment for constipation. ^{3 4 6 7 8}

Who Is on the Research Team?

Christopher P Cardozo, MD

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 bowel incontinence or constipation. The study aims to find a lower dose of medication that can help with bowel evacuation without the need for injections.

Inclusion Criteria

I have had a spinal cord injury for over a year.

I am either male or female.

I experience constipation or have trouble with bowel movements.

Exclusion Criteria

EKG abnormalities

My MoCA score is above 20, indicating I can make informed decisions.

I am currently on medication that affects my nerve system.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive Neostigmine and Glycopyrrolate by transdermal administration using a wired ION system to induce bowel evacuation

2 hours

1 visit (in-person)

Pharmacokinetic Monitoring

Pharmacokinetic studies are performed to measure plasma levels of Neostigmine and Glycopyrrolate

8 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including side-effects and bowel evacuation outcomes

1-2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Glycopyrrolate
• Neostigmine

Trial Overview The trial is testing a combination of two drugs, Neostigmine and Glycopyrrolate, administered through the skin using a device called I-Box by Dynatronics. It's focused on finding an effective dose that can be given transcutaneously.

How Is the Trial Designed?

Group I: Primary Experimental Treatment 2 Interventions

Subjects will receive medication administration intravenously, then through a wired ION system of NEO + GEO.

Who Is Running the Clinical Trial?

James J. Peters Veterans Affairs Medical Center

Lead Sponsor

Trials

59

Recruited

2,900+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/36064986/

Effect of neuromuscular reversal with neostigmine ... Conclusions: Patients who received sugammadex had a reduced time to achieving first stool and GI-2. Neostigmine use, bowel anastomoses and ...

2. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/95/NCT06351995/Prot_SAP_000.pdf

Neostigmine and Glycopyrrolate by Iontophoresis to Indu The investigators have developed a novel dual drug combination to elicit a safe and predictable bowel evacuation (BE). Objectives: Specific Aim: To determine a ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0952818024002174

Effects of neuromuscular block reversal with neostigmine ... Therefore, this study explored these effects in a randomized clinical trial, comparing how neostigmine/glycopyrrolate and sugammadex affect bowel function ...

4. mdpi.com mdpi.com/2077-0383/12/9/3235

The Postoperative Effect of Sugammadex versus ... Sugammadex reversal resulted in a significantly faster return of defecation or flatus after surgery compared to acetylcholinesterase inhibitors.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5604700/

Neostigmine and glycopyrronium This case demonstrates the novel use of neostigmine and glycopyrronium in decompression of the bowel in a patient with pseudo-obstruction.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4877263/

Evaluating the Safety and the Effects on Colonic ... Neostigmine significantly decreases colonic compliance in patients with refractory chronic constipation. Symptomatic bradycardia in response to neostigmine ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT06351995

Neostigmine and Glycopyrrolate by Iontophoresis | ... The data collected will include the presence or absence of bowel evacuation, time to bowel evacuation, consistency (Bristol stool scale), and quantity (by ...

8. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2023/216903s000lbl.pdf

PREVDUO (neostigmine - accessdata.fda.gov There are no studies on the safety of glycopyrrolate exposure during the period of organogenesis, and therefore, it is not possible to draw any conclusions on ...