Amifampridine for Botulism

Overseen By Mozhdeh Marandi

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Wake Forest University Health Sciences

Must not be taking: Pyridostigmine, Amifampridine

Disqualifiers: Cardiac arrhythmia, Seizures, Asthma, others

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

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 2

Duration: 2-3 hours

21 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial is testing if amifampridine can help improve muscle function in patients who have received BTX-A injections. Amifampridine works by boosting the signals between nerves and muscles. The goal is to see if it can counteract the muscle weakening effects of BTX-A.

Will I have to stop taking my current medications?

The trial requires that you stop taking pyridostigmine, as it can affect neuromuscular transmission. If you are using any investigational drug or device, you must stop at least 30 days before joining the trial.

What data supports the effectiveness of the drug Amifampridine for treating botulism?

The research on a similar drug, 3,4-diaminopyridine, showed it did not improve muscle strength or respiratory function in a patient with botulism, suggesting limited effectiveness for this type of treatment in botulism cases. ^{1 2 3 4 5}

How does the drug Amifampridine differ from other treatments for botulism?

Amifampridine (3,4-diaminopyridine) is unique because it can reverse muscle paralysis caused by botulism by enhancing nerve signal transmission, unlike standard treatments that mainly provide supportive care. It is the first small molecule shown to reverse systemic paralysis and improve survival in animal models of botulism, offering a novel approach beyond traditional antitoxin therapy. ^{4 6 7 8 9}

Research Team

James B Caress, MD

Principal Investigator

Wake Forest University Health Sciences

Eligibility Criteria

This trial is for adults aged 18-80 who have had Botox injections in facial muscles and are now looking to improve muscle function. They must be able to consent, not have a history of heart rhythm problems, seizures, severe asthma, liver or kidney disease, facial nerve issues, or use of investigational drugs recently.

Inclusion Criteria

I can make my own decisions and agree to study treatments and tests.

I am between 18 and 80 years old.

I received a Botox injection in my face with 100-200 units, 80-150 days ago.

Exclusion Criteria

I am currently taking pyridostigmine.

I have a history of irregular heartbeats.

I have a history of seizures or my asthma is not under control.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 week

Baseline Assessment

Baseline single fiber electromyography (SFEMG) is conducted before administration of amifampridine

1 day

1 visit (in-person)

Treatment

Amifampridine is orally administered, followed by post-dose SFEMG and observation

2-3 hours

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

Treatment Details

Interventions

• Amifampridine

Trial Overview The study tests if amifampridine can enhance muscle response in patients previously treated with Botox. Participants will receive the drug and undergo specialized muscle testing to measure any improvements in neuromuscular transmission.

Participant Groups

Group I: Amifampridine will be orally administered to study participants Experimental Treatment 1 Intervention

Amifampridine will be orally administered to study participants following completion of the baseline SFEMG. Post-dose SFEMG will commence at 30 minutes following dosing and will be completed within 30 minutes. The participant will remain under observation in the Diagnostic Neurology suite for 2 hours after dosing so it is estimated that the entire protocol including monitoring will be completed within 2-3 hours.

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

References

1. England pubmed.ncbi.nlm.nih.gov

Infant botulism: an underestimated threat. [2021]

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

Wound botulism in injection drug users: time to antitoxin correlates with intensive care unit length of stay. [2021]

3. Belgium pubmed.ncbi.nlm.nih.gov

Human type A botulism and treatment with 3,4-diaminopyridine. [2018]

4. England pubmed.ncbi.nlm.nih.gov

Iatrogenic Botulism Outbreak in Egypt due to a Counterfeit Botulinum Toxin A Preparation - A Descriptive Series of Patient Features and Outcome. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

[Botulism: Diagnosis and Therapy]. [2017]

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

Aminopyridines Restore Ventilation and Reverse Respiratory Acidosis at Late Stages of Botulism in Mice. [2023]

7. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Effect of 4-aminopyridine on the development of experimental botulism]. [2013]

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

A preclinical evaluation of aminopyridines as putative therapeutic agents in the treatment of botulism. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Antidotal treatment of botulism in rats by continuous infusion with 3,4-diaminopyridine. [2022]