Botox Injection for Preventing Pancreatic Fistula After Surgery

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: OHSU Knight Cancer Institute

Disqualifiers: Hypersensitivity to BTX, Infection, Serious cardiovascular disease, Neuromuscular disease, 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: 4

4 Participants Needed

Trial Summary

What is the purpose of this trial?

This phase II trial studies the effect of botulinum toxin (Botox) in preventing postoperative pancreatic fistula after distal pancreatectomy. Postoperative pancreatic fistula (POPF) is a known risk of distal pancreatic surgery, in which leakage of pancreatic digestive liquids causes internal swelling that can be painful (termed inflammation). A valve-like muscle, called the Sphincter of Oddi, opens and closes, controlling the flow of digestive liquids from the liver (bile) and pancreas (pancreatic juice) to the small intestine (duodenum). After surgery, the Sphincter of Oddi may act to block the flow of normal pancreatic secretions, causing secretions to leak into the abdomen resulting in POPF. Botox is a drug that can cause paralysis of muscles. Giving an injection of Botox into the sphincter of Oddi before distal pancreatic surgery may reduce leakage of digestive fluids and potential POPF.

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

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug Botulinum Toxin Type A in preventing pancreatic fistula after surgery?

Research suggests that injecting botulinum toxin into the sphincter of Oddi before surgery can significantly reduce the rate of pancreatic fistula, a common and serious complication after pancreatic surgery. ^{1 2 3 4 5}

Is Botox safe for preventing pancreatic fistula after surgery?

Botox (Botulinum Toxin Type A) has been used in various medical treatments and is generally considered safe, but there have been reports of serious side effects like difficulty swallowing, muscle weakness, and breathing problems when used for cosmetic purposes. The safety of Botox for preventing pancreatic fistula is still being studied, and early trials are looking into its safety and effectiveness for this specific use. ^{1 3 4 6 7}

How does the drug Botox prevent pancreatic fistula after surgery?

Botox is injected endoscopically into the sphincter of Oddi (a muscle controlling the flow of digestive juices) before surgery to prevent pancreatic fistula, a common complication after pancreatic surgery. This approach is unique because it targets the muscle to reduce pressure and leakage, unlike other treatments like octreotide, which have shown mixed results. ^{1 2 3 4 5}

Research Team

Brett C. Sheppard

Principal Investigator

OHSU Knight Cancer Institute

Eligibility Criteria

Adults scheduled for elective distal pancreatectomy or RAMPS who can understand the trial and consent to it. They must not be pregnant, have a negative pregnancy test, and use contraception until 14 days post-intervention. Exclusions include hypersensitivity to Botox, infection at injection site, recent acute pancreatitis, severe anesthesia risk (ASA score > III), liver cirrhosis, comprehension barriers, non-compliance risks, neuromuscular diseases increasing BTX risks.

Inclusion Criteria

I understand what joining this clinical trial means for me.

Written informed consent from participant or legally authorized representative

For participants of childbearing potential, a negative pregnancy test and adequate contraception until 14 days after trial intervention

Exclusion Criteria

I have previously received Botox treatments.

Your kidneys are not working well enough, based on a test called creatinine clearance.

Pregnancy or lactation

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Pre-operative Treatment

Patients receive botulinum toxin type A via endoscopic injection into intraduodenal sphincter of Oddi segment

1-2 weeks

1 visit (in-person)

Surgery

Planned distal pancreas resection

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

2 visits (in-person)

Treatment Details

Interventions

• Botulinum Toxin Type A

Trial Overview The trial is testing if injecting Botulinum Toxin Type A (Botox) into the Sphincter of Oddi before surgery can prevent pancreatic fistula by reducing digestive fluid leakage after a distal pancreatectomy. It's a phase II study aiming to see how effective this intervention is in preventing complications.

Participant Groups

Group I: Treatment of POPF (botulinum toxin type A) Experimental Treatment 1 Intervention

Patients receive botulinum toxin type A via endoscopic injection into intraduodenal sphincter of Oddi segment between 7-14 days prior to planned distal pancreas resection.

Botulinum Toxin Type A is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Botox for:

• Temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity
• Temporary improvement in the appearance of moderate to severe facial wrinkles and folds
• Axillary hyperhidrosis
• Blepharospasm
• Strabismus
• Cervical dystonia
• Chronic migraine
• Overactive bladder
• Detrusor overactivity associated with a neurologic condition

Approved in European Union as Botox for:

• Glabellar lines
• Facial wrinkles and folds
• Axillary hyperhidrosis
• Blepharospasm
• Strabismus
• Cervical dystonia
• Chronic migraine
• Overactive bladder
• Detrusor overactivity associated with a neurologic condition
• Spasticity of the upper limb

Approved in Canada as Botox for:

• Temporary improvement in the appearance of moderate to severe glabellar lines associated with corrugator and/or procerus muscle activity
• Temporary improvement in the appearance of moderate to severe facial wrinkles and folds
• Axillary hyperhidrosis
• Blepharospasm
• Strabismus
• Cervical dystonia
• Chronic migraine
• Overactive bladder
• Detrusor overactivity associated with a neurologic condition

Who Is Running the Clinical Trial?

OHSU Knight Cancer Institute

Lead Sponsor

Trials

239

Recruited

2,089,000+

Oregon Health and Science University

Collaborator

Trials

1,024

Recruited

7,420,000+

Findings from Research

A preoperative injection of botulinum toxin into the sphincter of Oddi was found to be a safe and effective method to significantly reduce the incidence of clinically relevant postoperative pancreatic fistulas after distal pancreatectomy, with no cases of grade B/C fistulas in the treatment group compared to 33% in the control group.

In a study involving 29 patients, the botulinum toxin injection was well-tolerated, with only one patient experiencing a temporary increase in serum amylase and lipase levels, indicating that this approach may help improve postoperative outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sphincter of Oddi botulinum toxin injection to prevent pancreatic fistula after distal pancreatectomy. Hackert, T., Klaiber, U., Hinz, U., et al.[2018]

A meta-analysis of 7 randomized controlled trials involving 1359 patients found that perioperative use of octreotide significantly reduces the incidence of postoperative pancreatic fistula after elective pancreatic surgery, with a relative risk of 0.59.

Despite the reduction in pancreatic fistula incidence, octreotide did not lead to a significant decrease in postoperative mortality, indicating that while it is effective in preventing one complication, it does not impact overall survival rates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of octreotide for the prevention of pancreatic fistula after elective pancreatic surgery: a systematic review and meta-analysis. Alghamdi, AA., Jawas, AM., Hart, RS.[2021]

In a study of 19 patients undergoing distal pancreatectomy, the endoscopic injection of botulinum toxin (BTX) into the sphincter of Oddi did not significantly reduce the incidence of clinically relevant postoperative pancreatic fistula (POPF) compared to a control group, with rates of 32% in the BTX group and 42% in the control group.

There were no complications related to the BTX injection, suggesting it is a safe procedure; however, the study's findings contradict previous reports of BTX's effectiveness, indicating a need for further research through randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reproducibility of preoperative endoscopic injection of botulinum toxin into the sphincter of Oddi to prevent postoperative pancreatic fistula. Volk, A., Distler, M., Müssle, B., et al.[2022]

The PREBOTPilot trial is a phase II clinical study involving 60 patients undergoing distal pancreatectomy, aiming to assess the safety and efficacy of preoperative botulinum toxin injection into the sphincter of Oddi to prevent postoperative pancreatic fistula (POPF).

The primary endpoint of the trial is to evaluate the occurrence of clinically relevant POPF and/or death within 30 days post-surgery, with secondary outcomes including postoperative complications and quality of life assessments up to 3 months after the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protocol of a randomised controlled phase II clinical trial investigating PREoperative endoscopic injection of BOTulinum toxin into the sphincter of Oddi to reduce postoperative pancreatic fistula after distal pancreatectomy: the PREBOTPilot trial. Klaiber, U., Sauer, P., Martin, E., et al.[2021]

Intrapyloric injection of botulinum toxin A (BoTx) significantly improved symptoms of diabetic gastroparesis (DGP) in three pancreas transplant patients, with effects lasting an average of 29 weeks after a single injection of 100 units.

The treatment was found to be safe and effective, with patients reporting improved quality of life, and some requiring additional doses after the initial effect wore off.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrapyloric injection of botulinum toxin a for the treatment of persistent gastroparesis following successful pancreas transplantation. Ben-Youssef, R., Baron, PW., Franco, E., et al.[2023]

Botulinum toxin type A shows potential efficacy in treating refractory gastroparesis, with some studies reporting improvements in gastric emptying and symptoms like nausea and abdominal pain, particularly in patients with diabetic gastroparesis.

Despite its potential benefits, botulinum toxin type A is not FDA-approved for this use, and responses vary, with about 43% of patients showing improvement; further large-scale trials are necessary to establish its effectiveness and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Botulinum toxin type A for treatment of refractory gastroparesis. DeSantis, ER., Huang, S.[2019]

Two cases of clinical botulism occurred in female patients after receiving botulinum toxin type A injections for cosmetic purposes, highlighting potential serious adverse reactions from these treatments.

Both patients showed clinical improvement after receiving botulinum antitoxin 7 and 9 days post-symptom onset, suggesting that antitoxin treatment may still be effective even when administered late.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Delayed Antitoxin Treatment of Two Adult Patients with Botulism after Cosmetic Injection of Botulinum Type A Toxin. Fan, KL., Wang, YL., Chu, G., et al.[2018]

References

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

Sphincter of Oddi botulinum toxin injection to prevent pancreatic fistula after distal pancreatectomy. [2018]

2. Canada pubmed.ncbi.nlm.nih.gov

Use of octreotide for the prevention of pancreatic fistula after elective pancreatic surgery: a systematic review and meta-analysis. [2021]

3. Germany pubmed.ncbi.nlm.nih.gov

Reproducibility of preoperative endoscopic injection of botulinum toxin into the sphincter of Oddi to prevent postoperative pancreatic fistula. [2022]

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

Protocol of a randomised controlled phase II clinical trial investigating PREoperative endoscopic injection of BOTulinum toxin into the sphincter of Oddi to reduce postoperative pancreatic fistula after distal pancreatectomy: the PREBOTPilot trial. [2021]

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

Intrapyloric injection of botulinum toxin a for the treatment of persistent gastroparesis following successful pancreas transplantation. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Botulinum toxin type A for treatment of refractory gastroparesis. [2019]

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

Delayed Antitoxin Treatment of Two Adult Patients with Botulism after Cosmetic Injection of Botulinum Type A Toxin. [2018]