Neostigmine for Colonic Pseudo-Obstruction

Overseen By Meghan Lewis, MD

Age: Any Age

Sex: Any

Trial Phase: Phase 4

Sponsor: University of Southern California

Must not be taking: Beta blockers, Prokinetics

Disqualifiers: Bradycardia, Hypotension, Bronchospasm, others

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

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 24 hours

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines the optimal method for administering neostigmine, a medication that stimulates muscle contractions, to treat acute colonic pseudo-obstruction—a blockage-like condition in the large intestine without a physical blockage. The trial compares two methods: a quick IV injection and a slower subcutaneous shot, to determine which is more effective with fewer side effects. Eligible participants must have a diagnosis confirmed by X-ray or CT scan and must not have any actual obstructions, certain heart issues, or other specific medical conditions. As a Phase 4 trial, this research aims to understand how this FDA-approved and effective treatment can benefit more patients.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you have taken prokinetic drugs like cisapride or metoclopramide in the 24 hours before evaluation.

What is the safety track record for Neostigmine?

A previous study found neostigmine to be a safe and effective treatment for acute colonic pseudo-obstruction when other treatments failed. The IV push method acts quickly but may cause more side effects. Research has shown that administering neostigmine subcutaneously appears safe, with no serious side effects reported. Both methods are effective, but their side effects may differ. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Unlike standard treatments for colonic pseudo-obstruction, which often involve decompression with a nasogastric tube or colonoscopy, neostigmine offers a pharmacological approach that can quickly resolve the issue. Neostigmine is unique because it enhances gastrointestinal motility by inhibiting the breakdown of acetylcholine, which stimulates muscle contractions in the colon. Researchers are particularly excited about this treatment because it can be administered either as a slow IV push or subcutaneously, offering flexibility in delivery and potentially faster relief. This could lead to a more efficient and less invasive treatment option, reducing the need for more invasive procedures.

What is the effectiveness track record for Neostigmine in treating colonic pseudo-obstruction?

Research has shown that neostigmine effectively treats acute colonic pseudo-obstruction, a condition where the colon appears blocked without a physical obstruction. In this trial, participants will receive neostigmine either through an IV push or a subcutaneous injection. Studies indicate that administering neostigmine via IV can prompt colon movement within 20-30 minutes, with about an 80% success rate. The subcutaneous route is also promising, with 93% of patients experiencing relief without serious side effects. Both methods are effective, but this trial aims to determine which one is more effective or has fewer side effects. Overall, neostigmine serves as a reliable treatment for this condition. ^{1 2 3 6 7}

Who Is on the Research Team?

Meghan Lewis, MD

Principal Investigator

University of Southern California

Are You a Good Fit for This Trial?

This trial is for patients with a condition called acute colonic pseudo obstruction, confirmed by imaging tests like X-rays or CT scans. Their cecal diameter should be over 9 cm or transverse colon over 6 cm, and they must not have any blockages further down the bowel.

Inclusion Criteria

My tests show no blockage in my lower intestine.

Patients with radiologically confirmed acute colonic pseudo obstruction (ACPO).

Plain abdominal radiograph or computed tomography imaging

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Treatment

Participants receive neostigmine via IV push or subcutaneous routes for up to 24 hours

24 hours

Continuous monitoring during treatment

Follow-up

Participants are monitored for recurrence of colonic pseudo obstruction and adverse reactions

7 days

What Are the Treatments Tested in This Trial?

Interventions

• Neostigmine

Trial Overview The study is testing two ways of giving Neostigmine to treat acute colonic pseudo obstruction: directly into the vein (IV push) and under the skin (subcutaneous). It aims to find out which method works best with fewer side effects.

How Is the Trial Designed?

Group I: subcutaneous Experimental Treatment 1 Intervention

1.0 mg subcutaneous repeated q8hr until resolution for up to 24 hours (3.0 mg total in 24 hours)

Group II: IV push Active Control 1 Intervention

2 mg slow intravenous injection over five minutes repeated q12hr until resolution for up to 24 hours. (4 mg total in 24 hours)

Neostigmine is already approved in United States, European Union, India for the following indications:

Approved in United States as Prostigmin for:

• Myasthenia Gravis
• Reversal of Neuromuscular Blockade
• Urinary Retention

Approved in European Union as Neostigmine for:

• Myasthenia Gravis
• Reversal of Nondepolarizing Muscle Relaxants

Approved in India as Neostigmine for:

• Myasthenia Gravis
• Reversal of Neuromuscular Blockade

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

Published Research Related to This Trial

In a study of 30 patients with acute colonic pseudo-obstruction (ACPO), subcutaneous neostigmine was found to be safe, with no serious complications like bradycardia reported during treatment.

The treatment resulted in a 93% success rate in resolving ACPO, suggesting that subcutaneous neostigmine can be as effective as intravenous neostigmine without the need for continuous cardiac monitoring.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Subcutaneous neostigmine appears safe and effective for acute colonic pseudo-obstruction (Ogilvie's syndrome). Frankel, A., Gillespie, C., Lu, CT., et al.[2020]

In a study of 18 patients with acute colonic pseudo-obstruction, intravenous neostigmine was effective in achieving rapid bowel decompression, with 75% of patients showing significant improvement after a single dose.

Neostigmine treatment helped avoid the need for surgical intervention, supporting the idea that excessive parasympathetic suppression contributes to Ogilvie's syndrome.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early resolution of Ogilvie's syndrome with intravenous neostigmine: a simple, effective treatment. Turégano-Fuentes, F., Muñoz-Jiménez, F., Del Valle-Hernández, E., et al.[2019]

In a study of 43 patients with acute colonic pseudo-obstruction (ACPO) who did not respond to conservative treatments, both neostigmine protocols (bolus dose and continuous infusion) showed similar effectiveness, with overall response rates of 80% for the bolus group and 69.6% for the continuous infusion group.

Both treatment protocols were safe, with only minor colonic complications observed in two patients and no major side effects requiring treatment cessation, indicating that neostigmine can be a reliable option for managing ACPO.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neostigmine treatment protocols applied in acute colonic pseudo-obstruction disease: A retrospective comparative study. İlban, Ö., Çiçekçi, F., Çelik, JB., et al.[2020]

Subcutaneous (SQ) administration of neostigmine is a safe and effective alternative for treating conditions like ileus and acute colonic pseudo-obstruction (ACPO), with a median time to first bowel movement of about 29 hours in a study of 182 patients.

The study reported a low incidence of adverse events (1.65%), primarily bradycardia, which resolved upon discontinuation of the drug, suggesting that while SQ neostigmine is generally safe, patients with certain heart conditions should be monitored closely.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Subcutaneous Neostigmine for Ileus, Acute Colonic Pseudo-obstruction, or Refractory Constipation. Kram, B., Greenland, M., Grant, M., et al.[2019]

Neostigmine appears to be a safe and effective treatment for postoperative acute colonic pseudo-obstruction (ACPO) after conservative treatments have failed, based on a review of various studies including one randomized controlled trial and multiple observational studies.

While neostigmine has shown improvements in clinical symptoms and reduced time to resolution for patients with ACPO, it is not currently recommended as a first-line treatment, highlighting the need for further prospective clinical trials to better define its role.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous neostigmine for postoperative acute colonic pseudo-obstruction. Elsner, JL., Smith, JM., Ensor, CR.[2022]

In a study of 10 children with acute colonic pseudo-obstruction (ACPO) due to hematologic malignancies, 80% responded positively to subcutaneous neostigmine treatment, showing improvement within a median of 29 hours.

Neostigmine was found to be effective in treating ACPO without causing significant cardiovascular side effects, indicating it is a safe option for this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neostigmine for the treatment of acute colonic pseudo-obstruction (ACPO) in pediatric hematologic malignancies. Lee, JW., Bang, KW., Jang, PS., et al.[2021]

In a study of 27 patients with acute colonic pseudo-obstruction, 84% responded to neostigmine treatment, with 63% of those showing a sustained response, indicating neostigmine is an effective option for this condition.

Patients who were postoperative were more likely to respond positively to neostigmine, while those with electrolyte imbalances or on anti-motility agents had a significantly poorer response, suggesting these factors should be considered when predicting treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors predicting successful outcome following neostigmine therapy in acute colonic pseudo-obstruction: a prospective study. Mehta, R., John, A., Nair, P., et al.[2013]

Intravenous neostigmine significantly reduces the duration of acute colonic pseudo-obstruction (ACPO) compared to conservative treatment, based on a review of ten studies, including seven prospective analyses.

While neostigmine is effective, it requires continuous cardiac monitoring due to the risk of bradycardia, which may necessitate treatment with atropine, highlighting the importance of safety measures during its administration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does neostigmine improve time to resolution of symptoms in acute colonic pseudo-obstruction? Kayani, B., Spalding, DR., Jiao, LR., et al.[2013]

Neostigmine was successfully used to treat colonic pseudo-obstruction in a 27-year-old burn patient after conservative treatments failed, leading to resolution of symptoms without adverse effects.

This case suggests that neostigmine may be a safe and effective alternative to surgical options like colonoscopy for managing colonic pseudo-obstruction in burn patients, provided that mechanical obstruction is ruled out.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neostigmine to relieve a suspected colonic pseudo-obstruction in a burn patient: a case-based review of the literature. Gebre-Giorgis, AA., Roderique, EJ., Stewart, D., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4284455/

Neostigmine for acute colonic pseudo-obstruction: A meta- ... Neostigmine is a safe and effective option for patients with ACPO who failed to respond to conservative management.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04951726

Neostigmine Route for Acute Colonic Pseudo Obstruction This study will compare the efficacy and side effect profile of 2 potential routes of administration: IV push and subcutaneous. Detailed Description. Acute ...

3. nejm.org nejm.org/doi/full/10.1056/NEJM199907153410301

Neostigmine for the Treatment of Acute Colonic Pseudo- ... Colonic distention may recur in up to 40 percent of patients despite initial decompression. The results of three uncontrolled studies suggest ...

4. journalonsurgery.org journalonsurgery.org/pdf/1172.pdf

Intravenous and Subcutaneous Administration of ... Subcutaneous neostigmine appears safe and effective for acute colonic pseudo- obstruction (Ogilvie's syndrome). ANZ Journal of Surgery. 2019;.

5. sciencedirect.com sciencedirect.com/science/article/pii/S1878788615000302

Ogilvie's syndrome–acute colonic pseudo-obstruction Neostigmine · a 2–2.5 mg IV bolus injected over 3–5 minutes results in colonic motility within 20–30 minutes with a success rate of 80% [27]. If success is not ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/22388328/

Intravenous neostigmine for postoperative acute colonic ... Neostigmine may be a safe and effective treatment option for postoperative ACPO; however, current data do not support its use as a first-line intervention.

7. emcrit.org emcrit.org/ibcc/oglivie/

Acute colonic pseudo-obstruction (ACPO - EMCrit Colonic pseudo-obstruction will usually respond nicely to prompt administration of IV neostigmine. The best approach is generally prompt medical ...