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The HepatoPancreaticoBiliary Resection Arginine Immunomodulation (PRIMe) Trial (PRIMe)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04549662
Recruitment Status : Recruiting
First Posted : September 16, 2020
Last Update Posted : June 9, 2022
Sponsor:
Collaborators:
Enhanced Medical Nutrition
Sunnybrook Health Sciences Centre Clinical Research Grant Competition
Sunnybrook Health Sciences Centre AFP Innovation Fund
Information provided by (Responsible Party):
Sunnybrook Health Sciences Centre

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
Hepatopancreaticobiliary (HPB) Malignancy Surgery Dietary Supplement: Active A Dietary Supplement: Active B Dietary Supplement: Lipid bolus Dietary Supplement: Placebo oil Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated 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 : June 16, 2021
Estimated Primary Completion Date : December 30, 2023
Estimated Study Completion Date : December 30, 2025

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Natural killer (NK) cell killing [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Day of surgery to 90-days after surgery ]
    Wound complications including dehiscence and infection will be diagnosed clinically.

  6. Length of stay [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04549662


Contacts
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Contact: Paul Karanicolas, MD PhD 416-480-4774 Paul.Karanicolas@sunnybrook.ca
Contact: Sonya Mergler 416-480-5627 sonya.mergler@sunnybrook.ca

Locations
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Canada, Ontario
The Ottawa Hospital - General Campus Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Guillaume Martel, MD    613-737-8899 ext 71053    gumartel@toh.ca   
Contact: Leah Monette       leamonette@ohri.ca   
Sunnybrook Health Sciences Centre Recruiting
Toronto, Ontario, Canada, M4N 3M5
Contact: Rachel Roke    416-480-6100 ext 85391    rachel.roke@sunnybrook.ca   
Principal Investigator: Paul Karanicolas         
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
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Responsible Party: Sunnybrook Health Sciences Centre
ClinicalTrials.gov Identifier: NCT04549662    
Other Study ID Numbers: 076-2017
First Posted: September 16, 2020    Key Record Dates
Last Update Posted: June 9, 2022
Last Verified: June 2022

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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:
immunomodulation
omega-3 fatty acids
arginine
Additional relevant MeSH terms:
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Neoplasms