The HepatoPancreaticoBiliary Resection Arginine Immunomodulation (PRIMe) Trial

Surgery Clinical Trial

— PRIMe  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04549662
• Other study ID #: 076-2017
• Status: Completed
• Phase: N/A
• Start date: June 16, 2021
• Est. completion date: February 12, 2024

Study information

• Verified date: October 2023
• Source: Sunnybrook Health Sciences Centre
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: February 12, 2024
• Est. primary completion date: February 12, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Neoplasms
• Surgery

Intervention

Dietary Supplement:
• Active A
Powdered formula containing whey protein and arginine
• Active B
Powdered formula containing whey protein
• Lipid bolus
Omega-3 fatty acids
• Placebo oil
Control placebo oil that does not contain omega-3 fatty acids

Locations

Country	Name	City	State
Canada	The Ottawa Hospital - General Campus	Ottawa	Ontario
Canada	Sunnybrook Health Sciences Centre	Toronto	Ontario

Sponsors (4)

Lead Sponsor	Collaborator
Sunnybrook Health Sciences Centre	Enhanced Medical Nutrition, Sunnybrook Health Sciences Centre AFP Innovation Fund, Sunnybrook Health Sciences Centre Clinical Research Grant Competition

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Natural killer (NK) cell killing	Reduction in NK cell killing as measured on post-operative day one (POD1) as compared to baseline (pre-operative) between the control and experimental cohorts. Nutritional supplementation will be considered effective at reducing postoperative NK cell dysfunction if there is a 50% or greater improvement in postoperative suppression of NK cell cytotoxicity (reduction of 27% from baseline).	Post-operative day 1 (Day 1) as compared to baseline (pre-operative)
Secondary	Secondary immune function outcomes: Immune cell subsets	Flow cytometric analysis of different immune cell subsets to compare their proportions at all time points.	Day of surgery to 30-days after surgery
Secondary	Secondary immune function outcomes: NK cell activating and inhibitory receptors	Flow cytometric characterization of NK cell activating and inhibitory receptors to assess whether they are affected by immunosupplementation.	Day of surgery to 30-days after surgery
Secondary	Secondary immune function outcomes: amino acid levels	Systemic blood levels of amino acids will be measured via liquid chromatography-mass spectrometry protein card analysis.	Day of surgery to 30-days after surgery
Secondary	Incidence of pancreatic fistula	Pancreatic fistula of International Study Group on Pancreatic Fistula (ISGPF) Grade B & C (i.e. clinically significant) will be diagnosed clinically.	Day of surgery to 90-days after surgery
Secondary	Postoperative wound complication and surgical site infection	Wound complications including dehiscence and infection will be diagnosed clinically.	Day of surgery to 90-days after surgery
Secondary	Length of stay	Length of stay will be measured as number of days from admission to discharge.	Day of surgery to day of discharge after surgery, assessed until day of discharge after surgery occurs
Secondary	90-day postoperative complications (Clavien-Dindo 3-5)	Postoperative complications with Clavien-Dindo Grades 3-5 (i.e. requiring procedural intervention or ICU admission, or causing death) will be recorded.	Day of surgery to 90-days after surgery
Secondary	90-day postoperative mortality	The incidence of readmission within 90 days of surgery will be recorded as the number of days associated with each re-admission.; Death within 90 days of surgery will be considered complications of the surgery.	Day of surgery to 90-days after surgery
Secondary	Incidence of liver insufficiency	Posthepatectomy liver failure of International Study Group of Liver Surgery (ISGLS) Grade B & C (i.e. clinically significant) will be diagnosed clinically	Day of surgery to 90-days after surgery