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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether Botox (Botulinum Toxin Type A) can prevent leaks of digestive fluids after certain pancreatic surgeries. Post-surgery, some individuals experience leaks due to issues with a muscle that controls fluid flow. Botox may relax this muscle, reducing the likelihood of leaks and associated pain. Individuals scheduled for specific types of pancreatic surgery might be suitable candidates for this study. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of participants.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that botulinum toxin type A, commonly known as Botox, is safe for use in the body. Studies have found that injecting Botox into the sphincter of Oddi—a muscle that controls the flow of digestive juices—can help relax it. This method has proven effective for people with sphincter of Oddi dysfunction, a condition where the muscle doesn't open properly.

Botox has also been studied for preventing pancreatic fistulas, which are leaks of digestive fluids after surgery. One study found that injecting Botox before surgery safely lowered the risk of developing a fistula.

Overall, Botox is well-tolerated and has a strong safety record, making it a promising option for preventing complications after pancreas surgery. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for preventing pancreatic fistula, which often involve surgical techniques and postoperative care, botulinum toxin type A offers a unique approach by relaxing the sphincter of Oddi. This relaxation can potentially reduce the pressure in the pancreas and lower the risk of fistula formation after surgery. Researchers are excited because this method involves a minimally invasive endoscopic injection, which may provide a safer and more efficient way to prevent complications, potentially leading to quicker recovery times and improved outcomes for patients.

What evidence suggests that Botox might be an effective treatment for preventing pancreatic fistula?

This trial will investigate the use of botulinum toxin (Botox) to prevent pancreatic fistula after surgery. Participants will receive botulinum toxin type A via endoscopic injection into the Sphincter of Oddi. Studies have shown that Botox can relax muscles by temporarily stopping them from working. In this trial, injecting Botox into the Sphincter of Oddi (a muscle that acts like a valve) may help lower the risk of digestive fluids leaking into the abdomen after surgery, a common issue. Previous research found that Botox injections were generally safe, with most patients not experiencing major side effects. This treatment aims to reduce the chance of painful problems after pancreatic surgery by helping digestive juices flow properly. ^{1 3 6 7 8}

Who Is on the Research Team?

Brett C. Sheppard

Principal Investigator

OHSU Knight Cancer Institute

Are You a Good Fit for This Trial?

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 for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/27865590/

Sphincter of Oddi botulinum toxin injection to prevent ... End points were the feasibility, safety, and postoperative outcomes, including postoperative pancreatic fistula within 30 days after distal ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04220931

NCT04220931 | Intrapapillary Botulinum Toxin Injection for ... Intrapapillary botulinum toxin injection is believed to induce relaxation of the pancreatic sphincter, leading to a " pharmacological " pancreatic ...

3. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2021-06239

Endoscopic Botulinum Toxin Injection in the Prevention of ... This phase II trial studies the effect of botulinum toxin (Botox) in preventing postoperative pancreatic fistula after distal pancreatectomy.

4. clinicaltrials.eu clinicaltrials.eu/trial/study-on-botulinum-toxin-type-a-to-prevent-pancreatic-fistulas-in-patients-undergoing-distal-pancreatectomy/

Study on Botulinum Toxin Type A to Prevent Pancreatic ... This clinical trial investigates the use of Botulinum Toxin Type A (BOTOX®) for the prevention of postoperative pancreatic fistulas in patients undergoing ...

5. withpower.com withpower.com/trial/phase-3-pancreatic-fistula-8-2021-8dc2b

Botox Injection for Preventing Pancreatic Fistula After Surgery 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 ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6754046/

Reproducibility of preoperative endoscopic injection ... BTX induces muscle relaxation and has been used as a safe and effective treatment option in patients with sphincter of Oddi dysfunction. Recently, Hackert et al ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12427430/

A Review of Post-Operative Pancreatic Fistula Following ... In this review, we present the latest data on patient risk factors for developing POPF, such as obesity, smoking, young age, thick pancreas, ...

8. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0039606016305050

Sphincter of Oddi botulinum toxin injection to prevent ... Preoperative sphincter of Oddi botulinum toxin injection is a novel and safe approach to decrease the incidence of clinically relevant postoperative pancreatic ...