The HepatoPancreaticoBiliary Resection Arginine Immunomodulation (PRIMe) Trial

Sponsor
Sunnybrook Health Sciences Centre (Other)
Overall Status
Recruiting
CT.gov ID
NCT04549662
Collaborator
Enhanced Medical Nutrition (Industry), Sunnybrook Health Sciences Centre Clinical Research Grant Competition (Other), Sunnybrook Health Sciences Centre AFP Innovation Fund (Other)
45
2
3
54.5
22.5
0.4

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Dietary Supplement: Active A
  • Dietary Supplement: Active B
  • Dietary Supplement: Lipid bolus
  • Dietary Supplement: Placebo oil
N/A

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.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
45 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
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
Actual Study Start Date :
Jun 16, 2021
Anticipated Primary Completion Date :
Dec 30, 2023
Anticipated Study Completion Date :
Dec 30, 2025

Arms and Interventions

Arm Intervention/Treatment
Experimental: Group A

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
Powdered formula containing whey protein and arginine

Dietary Supplement: Lipid bolus
Omega-3 fatty acids

Active Comparator: Group B

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
Powdered formula containing whey protein and arginine

Dietary Supplement: Placebo oil
Control placebo oil that does not contain omega-3 fatty acids

Placebo Comparator: 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
Powdered formula containing whey protein

Dietary Supplement: Placebo oil
Control placebo oil that does not contain omega-3 fatty acids

Outcome Measures

Primary Outcome Measures

  1. Natural killer (NK) cell killing [Post-operative day 1 (Day 1) as compared to baseline (pre-operative)]

    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).

Secondary Outcome Measures

  1. Secondary immune function outcomes: Immune cell subsets [Day of surgery to 30-days after surgery]

    Flow cytometric analysis of different immune cell subsets to compare their proportions at all time points.

  2. Secondary immune function outcomes: NK cell activating and inhibitory receptors [Day of surgery to 30-days after surgery]

    Flow cytometric characterization of NK cell activating and inhibitory receptors to assess whether they are affected by immunosupplementation.

  3. Secondary immune function outcomes: amino acid levels [Day of surgery to 30-days after surgery]

    Systemic blood levels of amino acids will be measured via liquid chromatography-mass spectrometry protein card analysis.

  4. Incidence of pancreatic fistula [Day of surgery to 90-days after surgery]

    Pancreatic fistula of International Study Group on Pancreatic Fistula (ISGPF) Grade B & C (i.e. clinically significant) will be diagnosed clinically.

  5. Postoperative wound complication and surgical site infection [Day of surgery to 90-days after surgery]

    Wound complications including dehiscence and infection will be diagnosed clinically.

  6. Length of stay [Day of surgery to day of discharge after surgery, assessed until day of discharge after surgery occurs]

    Length of stay will be measured as number of days from admission to discharge.

  7. 90-day postoperative complications (Clavien-Dindo 3-5) [Day of surgery to 90-days after surgery]

    Postoperative complications with Clavien-Dindo Grades 3-5 (i.e. requiring procedural intervention or ICU admission, or causing death) will be recorded.

  8. 90-day postoperative mortality [Day of surgery to 90-days after surgery]

    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.

  9. Incidence of liver insufficiency [Day of surgery to 90-days after surgery]

    Posthepatectomy liver failure of International Study Group of Liver Surgery (ISGLS) Grade B & C (i.e. clinically significant) will be diagnosed clinically

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

Contacts and Locations

Locations

Site City State Country Postal Code
1 The Ottawa Hospital - General Campus Ottawa Ontario Canada K1H 8L6
2 Sunnybrook Health Sciences Centre Toronto Ontario Canada M4N 3M5

Sponsors and Collaborators

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

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier:
NCT04549662
Other Study ID Numbers:
  • 076-2017
First Posted:
Sep 16, 2020
Last Update Posted:
Jun 9, 2022
Last Verified:
Jun 1, 2022
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Sunnybrook Health Sciences Centre
Additional relevant MeSH terms:

Study Results

No Results Posted as of Jun 9, 2022