Neostigmine for Colonic Pseudo-Obstruction

Overseen by Meghan Lewis, MD

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 4

Recruiting

Sponsor: University of Southern California

Must not be taking: Beta blockers, Prokinetics

Disqualifiers: Bradycardia, Hypotension, Bronchospasm, others

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial tests neostigmine, a drug that helps reduce severe bloating in the colon, on patients with acute colonic pseudo-obstruction. It compares two methods of giving the drug: directly into a vein and under the skin, to see which is safer and more effective.

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 data supports the effectiveness of the drug Neostigmine for treating colonic pseudo-obstruction?

Research shows that Neostigmine is effective in resolving acute colonic pseudo-obstruction, especially when other treatments don't work. Studies have found it to be a safe and effective option for this condition, with successful outcomes reported in various cases. ^{1 2 3 4 5}

Is neostigmine safe for treating colonic pseudo-obstruction?

Neostigmine is generally safe for treating colonic pseudo-obstruction, but it can cause bradycardia (slow heart rate), which may need treatment with atropine. Patients receiving intravenous neostigmine should have continuous heart monitoring to watch for this side effect. ^{1 3 6 7 8}

How is the drug Neostigmine unique in treating colonic pseudo-obstruction?

Neostigmine is unique because it is an acetylcholinesterase inhibitor, which means it helps increase bowel movement by preventing the breakdown of a chemical that stimulates muscle contractions. It is often used when other treatments fail and can be administered intravenously or subcutaneously, offering flexibility in treatment options. ^{1 2 5 7 9}

Research Team

Meghan Lewis, MD

Principal Investigator

University of Southern California

Eligibility Criteria

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

Trial Timeline

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

Treatment Details

Interventions

• Neostigmine (Cholinesterase Inhibitor)

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.

Participant Groups

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 India for the following indications:

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+

Dr. Samir A.

University of Southern California

Chief Executive Officer since 2024

PhD in Molecular Biology from the University of Southern California

Dr. Chung

University of Southern California

Chief Medical Officer since 2016

MD from UC San Diego

Findings from Research

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]

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]

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 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 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]

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]

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 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]

References

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

Neostigmine to relieve a suspected colonic pseudo-obstruction in a burn patient: a case-based review of the literature. [2021]

2. Turkey pubmed.ncbi.nlm.nih.gov

Neostigmine treatment protocols applied in acute colonic pseudo-obstruction disease: A retrospective comparative study. [2020]

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

Intravenous neostigmine for postoperative acute colonic pseudo-obstruction. [2022]

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

Early resolution of Ogilvie's syndrome with intravenous neostigmine: a simple, effective treatment. [2019]

5. Australia pubmed.ncbi.nlm.nih.gov

Factors predicting successful outcome following neostigmine therapy in acute colonic pseudo-obstruction: a prospective study. [2013]

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

Does neostigmine improve time to resolution of symptoms in acute colonic pseudo-obstruction? [2013]

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

Efficacy and Safety of Subcutaneous Neostigmine for Ileus, Acute Colonic Pseudo-obstruction, or Refractory Constipation. [2019]

8. Australia pubmed.ncbi.nlm.nih.gov

Subcutaneous neostigmine appears safe and effective for acute colonic pseudo-obstruction (Ogilvie's syndrome). [2020]

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

Neostigmine for the treatment of acute colonic pseudo-obstruction (ACPO) in pediatric hematologic malignancies. [2021]