Clinical trial NCT04549662: The HepatoPancreaticoBiliary Resection Arginine Immunomodulation (PRIMe) Trial
Official title: The HepatoPancreaticoBiliary Resection Arginine Immunomodulation (PRIMe) Trial: A Randomized Phase II Trial of the Impact of Perioperative Immunomodulation on Immune Function Following Resection for HepatoPancreaticoBiliary Malignancy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hepatopancreaticobiliary (HPB) Malignancy
Surgery
Keywords: immunomodulation
omega-3 fatty acids
arginine
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: Enhanced Medical Nutrition
name: Sunnybrook Health Sciences Centre Clinical Research Grant Competition
name: Sunnybrook Health Sciences Centre AFP Innovation Fund
First posted: 2020-09-16
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a randomized controlled blinded superiority trial to evaluate the impact of perioperative immunosupplementation on immune function following resection for hepatopancreaticobiliary (HPB) malignancy.

Detailed description: This is a 1:1:1 randomized controlled blinded superiority trial to evaluate the impact of perioperative immunosupplementation on immune function following resection for hepatopancreaticobiliary (HPB) malignancy. Two variations of immunosupplementation will be compared to control nutritional supplement containing whey protein with an additional teaspoon (tsp) of placebo oil. These variations will be 1) a powdered formula containing whey protein and arginine (Active A) with an additional tsp of lipid bolus containing omega-3 fatty acids, and 2) a powdered formula containing whey protein and arginine (Active A) with an additional tsp of placebo oil which does not contain omega-3 fatty acids. The control nutritional supplement will be a powdered formula containing whey protein with an additional tsp of placebo oil.

Eligibility criteria: Inclusion Criteria:

* Patients age 18 and over at time of diagnosis
* Resectable presumed liver, pancreas, or bile duct malignancy (i.e., liver metastases, HCC, cholangiocarcinoma, pancreatic or periampullary adenocarcinoma, NETs)as determined by surgeon in clinic
* Anticipated hospital stay at least three days post-surgery
* Ability to tolerate oral intake and comply with protocol requirements

Exclusion Criteria:

* Documented significant immunodeficiency due to underlying illness (e.g. HIV/AIDS) and/or medication (e.g. systemic corticosteroids, azathioprine, cyclosporin A). Subjects may be on physiologic doses of replacement prednisone or equivalent doses of corticosteroid (\<7.5 mg daily)
* Subjects with resting hypotension (BP \<90/50 at rest)
* History of autoimmune disease, such as but not restricted to, inflammatory bowel disease, systemic lupus erythematosus, ankylosing spondylitis, scleroderma, or multiple sclerosis
* Serious, active, intercurrent chronic or acute illness, or other active illness considered by the investigator as an unwarranted high risk for an investigational product
* Active infection of any site and/or active herpes requiring ongoing treatment
* Known pregnancy or nursing mothers
* Subjects with an allergy to the nutritional supplement or comparator including milk, fish and/or shellfish allergies
* Subjects with religious or other objections to consuming fish or shellfish
* Subjects with severe asthma defined as asthma not controlled with inhaled corticosteroids and additional controllers or by oral corticosteroid treatment (arginine can cause allergic response or make swelling in airways worse)
* Subjects with a known inherited guanidinoacetate methyltransferase deficiency (due to an inability to convert arginine to creatine)
* Subject with known current liver cirrhosis
* Subjects with documented myocardial infarction or life-threatening arrhythmia
* Subjects with known current cardiac failure or coronary artery disease causing unstable angina

Primary outcomes:
measure: Natural killer (NK) cell killing
timeFrame: Post-operative day 1 (Day 1) as compared to baseline (pre-operative)
Secondary outcomes:
measure: Secondary immune function outcomes: Immune cell subsets
timeFrame: Day of surgery to 30-days after surgery
measure: Secondary immune function outcomes: NK cell activating and inhibitory receptors
timeFrame: Day of surgery to 30-days after surgery
measure: Secondary immune function outcomes: amino acid levels
timeFrame: Day of surgery to 30-days after surgery
measure: Incidence of pancreatic fistula
timeFrame: Day of surgery to 90-days after surgery
measure: Postoperative wound complication and surgical site infection
timeFrame: Day of surgery to 90-days after surgery
measure: Length of stay
timeFrame: Day of surgery to day of discharge after surgery, assessed until day of discharge after surgery occurs
measure: 90-day postoperative complications (Clavien-Dindo 3-5)
timeFrame: Day of surgery to 90-days after surgery
measure: 90-day postoperative mortality
timeFrame: Day of surgery to 90-days after surgery
measure: Incidence of liver insufficiency
timeFrame: Day of surgery to 90-days after surgery
Other outcomes:
Locations:
city: Ottawa
country: Canada
facility: The Ottawa Hospital - General Campus
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Centre
name: Paul Karanicolas, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: