Neostigmine + Atropine for Post-Dural Puncture Headache

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2

Sponsor: Mayo Clinic

Disqualifiers: Migraine, Asthma, Arrhythmia, 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

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 24 hours

18 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests if two medications, neostigmine and glycopyrrolate, can help new mothers with severe headaches caused by a spinal puncture during childbirth. The treatment aims to reduce the need for a more invasive procedure. Neostigmine increases brain fluid and tightens blood vessels to relieve pain, while glycopyrrolate reduces side effects.

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.

What data supports the effectiveness of the drug combination Neostigmine and Atropine for treating post-dural puncture headache?

Research suggests that using neostigmine with atropine shortly after a dural puncture can help reduce the occurrence and severity of headaches that often follow spinal anesthesia. Additionally, neostigmine has been shown to provide pain relief in other settings, which supports its potential effectiveness in this combination. ^{1 2 3 4 5}

Is the combination of Neostigmine and Atropine safe for humans?

Research shows that Neostigmine, even when combined with preservatives like methyl- and propylparabens, is generally safe for humans, although it may cause side effects like nausea and sedation. Studies in animals and humans have not shown significant neurotoxicity, supporting its safety in the doses studied. ^{1 2 3 4 6}

How is the drug combination of Neostigmine and Atropine unique for treating post-dural puncture headache?

The combination of Neostigmine and Atropine is unique for treating post-dural puncture headache because it is administered intravenously shortly after the dural puncture, aiming to reduce the incidence and severity of the headache over a five-day period, which is different from other treatments that may not focus on this specific timing or combination. ^{1 3 5 7 8}

Research Team

Mark Rollins, MD, PhD

Principal Investigator

Mayo Clinic

Eligibility Criteria

This trial is for postpartum women who developed a headache within 72 hours after delivery, specifically due to an accidental dural puncture during epidural analgesia. It's not suitable for those with asthma, heart issues like block or arrhythmias, inability to understand pain scores or speak English, fever over 38.5 C, refusal to participate, contraindications to certain pain relievers, history of migraines or myasthenia gravis.

Inclusion Criteria

You experienced a headache within 72 hours after giving birth.

You have a headache after a specific type of needle was used for pain relief during childbirth, and there is no other reason for the headache.

Exclusion Criteria

You have asthma.

Your pain score is less than 4 on a scale from 0 to 10.

You have a condition called heart block.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1-2 days

In-hospital assessment

Treatment

Participants receive IV administration of neostigmine and glycopyrrolate for PDPH treatment

Up to 24 hours

Continuous monitoring during hospital stay

Follow-up

Participants are monitored for safety and effectiveness after treatment

2 weeks

Daily in-hospital monitoring, followed by weekly check-ins

Treatment Details

Interventions

• Atropine
• Neostigmine

Trial Overview The study tests Neostigmine and Glycopyrrolate as treatments for headaches following dural puncture in new mothers. The goal is to see if these drugs can reduce the need for an epidural blood patch in women who got headaches after the needle used during labor caused a puncture.

Participant Groups

Group I: Postpartum dural puncture headache following dural puncture from Tuohy needle Experimental Treatment 2 Interventions

Subjects identified as experienced a post dural puncture headache after a confirmed dural puncture from a Tuohy needle will receive an IV administration of the study medications neostigmine and glycopyrrolate.

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

Approved in United States as Atropine for:

• Uveitis
• Pupillary dilation
• Refraction assessment
• Amblyopia
• Cycloplegia

Approved in Canada as Atropine for:

• Uveitis
• Pupillary dilation
• Refraction assessment
• Amblyopia
• Cycloplegia

Who Is Running the Clinical Trial?

Mayo Clinic

Lead Sponsor

Trials

3,427

Recruited

3,221,000+

References

1. India pubmed.ncbi.nlm.nih.gov

Evaluation of the Preventive Effects of Neostigmine Plus Atropine on Post-Dural Puncture Headache. [2023]

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

Use of intrathecal neostigmine as an adjunct to other spinal medications in perioperative and peripartum analgesia: a meta-analysis. [2022]

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

The efficacy of intrathecal neostigmine, intrathecal morphine, and their combination for post-cesarean section analgesia. [2022]

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

Phase I human safety assessment of intrathecal neostigmine containing methyl- and propylparabens. [2019]

5. India pubmed.ncbi.nlm.nih.gov

Comparative evaluation of different doses of intrathecal neostigmine as an adjuvant to bupivacaine for postoperative analgesia. [2022]

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

Studies on the safety of glucose and paraben-containing neostigmine for intrathecal administration. [2019]

7. China pubmed.ncbi.nlm.nih.gov

[Study on the mechanism of antinociception of intrathecal neostigmine in the formalin test in rats]. [2013]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Determination of neostigmine in human plasma and cerebrospinal fluid by high-performance liquid chromatography with ultraviolet detection. [2019]