The HepatoPancreaticoBiliary Resection Arginine Immunomodulation (PRIMe) Trial

NCT04549662 | Completed DMC

• 1 other identifier: 076-2017
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 2

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.

Conditions

Hepatopancreaticobiliary (HPB) Malignancy; Surgery

Keywords

immunomodulation; omega-3 fatty acids; arginine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• Secondary immune function outcomes: Immune cell subsets

  Day of surgery to 30-days after surgery

• Secondary immune function outcomes: NK cell activating and inhibitory receptors

  Day of surgery to 30-days after surgery

• Secondary immune function outcomes: amino acid levels

  Day of surgery to 30-days after surgery

• Incidence of pancreatic fistula

  Day of surgery to 90-days after surgery

• Postoperative wound complication and surgical site infection

  Day of surgery to 90-days after surgery

Study Arms (3)

Group A

EXPERIMENTAL

Powdered formula containing whey protein and arginine (Active A) and lipid bolus containing omega 3 fatty acids. Participants will mix the powder (Active A) with 250 mL of water and drink the formula 3 times per day for 5 days. Each drink will be followed by consuming 1 tsp of the lipid bolus. This will be done for 5 days prior to the operation and for 5 days after the operation.

Dietary Supplement: Active A; Dietary Supplement: Lipid bolus

Group B

ACTIVE COMPARATOR

Powdered formula containing whey protein and arginine (Active A) and placebo oil. Participants will mix the powder (Active A) with 250 mL of water and drink the formula 3 times per day for 5 days. Each drink will be followed by consuming 1 tsp of the lipid bolus. This will be done for 5 days prior to the operation and for 5 days after the operation.

Dietary Supplement: Active A; Dietary Supplement: Placebo oil

Comparator

PLACEBO COMPARATOR

Powdered formula containing whey protein (Active B) and placebo oil. Participants will mix the powder (Active B) with 250 mL of water and drink the formula 3 times per day for 5 days. Each drink will be followed by consuming 1 tsp of the lipid bolus. This will be done for 5 days prior to the operation and for 5 days after the operation.

Dietary Supplement: Active B; Dietary Supplement: Placebo oil

Interventions

Active A DIETARY_SUPPLEMENT

Powdered formula containing whey protein and arginine

Group A; Group B

Active B DIETARY_SUPPLEMENT

Powdered formula containing whey protein

Comparator

Lipid bolus DIETARY_SUPPLEMENT

Omega-3 fatty acids

Group A

Placebo oil DIETARY_SUPPLEMENT

Control placebo oil that does not contain omega-3 fatty acids

Comparator; Group B

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• Enhanced Medical Nutrition: collaborator
• Sunnybrook Health Sciences Centre Clinical Research Grant Competition: collaborator
• Sunnybrook Health Sciences Centre AFP Innovation Fund: collaborator

Study Sites (2)

The Ottawa Hospital - General Campus

Ottawa, Ontario, K1H 8L6, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Related Publications (1)

• Behman R, Auer RC, Bubis L, Xu G, Coburn NG, Martel G, Hallet J, Balaa F, Law C, Bertens KA, Abou Khalil J, Karanicolas PJ. Hepatopancreaticobiliary Resection Arginine Immunomodulation (PRIMe) trial: protocol for a randomised phase II trial of the impact of perioperative immunomodulation on immune function following resection for hepatopancreaticobiliary malignancy. BMJ Open. 2024 Apr 5;14(4):e072159. doi: 10.1136/bmjopen-2023-072159.

  PMID: 38580363 DERIVED

MeSH Terms

Conditions

Neoplasms

Study Officials

• Paul Karanicolas, MD, PhD

  Sunnybrook Health Sciences Centre

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2020
• First Posted: September 16, 2020
• Study Start: June 16, 2021
• Primary Completion: February 12, 2024
• Study Completion: February 12, 2024
• Last Updated: April 3, 2024

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)