Hepatopancreaticobiliary (HPB) MalignancyPRIMeNCT04549662
The HepatoPancreaticoBiliary Resection Arginine Immunomodulation (PRIMe) Trial
A study testing Active A, Active B and Lipid bolus in people with Hepatopancreaticobiliary (HPB) Malignancy and Surgery, run by Sunnybrook Health Sciences Centre at 2 sites in Canada.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hepatopancreaticobiliary (HPB) Malignancy, Surgery
- What is being tested?
- Active A, Active B and Lipid bolus
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 2 sitesCanada
- Study dates
- 16 Jun 2021to 12 Feb 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 13Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
The Ottawa Hospital - General Campus
Ottawa, Ontario, K1H 8L6
Sunnybrook Health Sciences Centre
Toronto, Ontario, M4N 3M5
About this study
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
This is a randomized controlled blinded superiority trial to evaluate the impact of perioperative immunosupplementation on immune function following resection for hepatopancreaticobiliary (HPB) malignancy.
Read the 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.
- Conditions
- Hepatopancreaticobiliary (HPB) Malignancy, Surgery
- Being tested
- Active A, Active B, Lipid bolus, Placebo oil
- Keywords
- immunomodulation, omega-3 fatty acids, arginine
- Medical subject headings
- Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active ADietary supplement
Powdered formula containing whey protein and arginine
Active BDietary supplement
Powdered formula containing whey protein
Lipid bolusDietary supplement
Omega-3 fatty acids
Placebo oilDietary supplement
Control placebo oil that does not contain omega-3 fatty acids
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: 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. Receives: Dietary Supplement: Active B; Dietary Supplement: Placebo oil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Post-operative day 1 (Day 1) as compared to baseline (pre-operative)
Secondary outcomes (9)
Secondary immune function outcomes: Immune cell subsets
Flow cytometric analysis of different immune cell subsets to compare their proportions at all time points.
Measured: Day of surgery to 30-days after surgery
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.
Measured: Day of surgery to 30-days after surgery
Secondary immune function outcomes: amino acid levels
Systemic blood levels of amino acids will be measured via liquid chromatography-mass spectrometry protein card analysis.
Measured: Day of surgery to 30-days after surgery
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.
Measured: Day of surgery to 90-days after surgery
Postoperative wound complication and surgical site infection
Wound complications including dehiscence and infection will be diagnosed clinically.
Measured: Day of surgery to 90-days after surgery
Length of stay
Length of stay will be measured as number of days from admission to discharge.
Measured: Day of surgery to day of discharge after surgery, assessed until day of discharge after surgery occurs
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.
Measured: Day of surgery to 90-days after surgery
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.
Measured: Day of surgery to 90-days after surgery
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
Measured: Day of surgery to 90-days after surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2020
- Study start16 Jun 2021
- Primary completion12 Feb 2024
- Study completion12 Feb 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hepatopancreaticobiliary (HPB) MalignancyStudies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Collaborators
- Enhanced Medical Nutrition
- Responsible party
- Sponsor
- Investigators
- Paul Karanicolas, MD, PhD, Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04549662
- Sponsor's protocol ID
- 076-2017
- Acronym
- PRIMe
- Status last verified
- Oct 2023
- First submitted
- 14 Aug 2020
- Last updated
- 3 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 38580363
Study at a glance
From the registry record, last updated by the sponsor on 3 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04549662
- Acronym / sponsor ID
- PRIMe / 076-2017
- Conditions
- Hepatopancreaticobiliary (HPB) Malignancy, Surgery
- Keywords
- immunomodulation, omega-3 fatty acids, arginine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Collaborators
- Enhanced Medical Nutrition
- Study start
- 16 Jun 2021 (actual)
- Primary completion
- 12 Feb 2024 (actual)
- Study completion
- 12 Feb 2024 (actual)
- First posted
- 16 Sep 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group A | Experimental | Dietary Supplement: Active A, Dietary Supplement: Lipid bolusPowdered 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. |
| Group B | Active comparator | Dietary Supplement: Active A, Dietary Supplement: Placebo oilPowdered 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. |
| Comparator | Placebo comparator | Dietary Supplement: Active B, Dietary Supplement: Placebo oilPowdered 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active APowdered formula containing whey protein and arginine | Dietary supplement | Group A, Group B |
| Active BPowdered formula containing whey protein | Dietary supplement | Comparator |
| Lipid bolusOmega-3 fatty acids | Dietary supplement | Group A |
| Placebo oilControl placebo oil that does not contain omega-3 fatty acids | Dietary supplement | Comparator, Group B |
Primary outcome
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).
9 secondary outcomes
Secondary immune function outcomes: Immune cell subsets
Time frame: Day of surgery to 30-days after surgery
Secondary immune function outcomes: NK cell activating and inhibitory receptors
Time frame: Day of surgery to 30-days after surgery
Secondary immune function outcomes: amino acid levels
Time frame: Day of surgery to 30-days after surgery
Incidence of pancreatic fistula
Time frame: Day of surgery to 90-days after surgery
Postoperative wound complication and surgical site infection
Time frame: Day of surgery to 90-days after surgery
Length of stay
Time frame: Day of surgery to day of discharge after surgery, assessed until day of discharge after surgery occurs
90-day postoperative complications (Clavien-Dindo 3-5)
Time frame: Day of surgery to 90-days after surgery
90-day postoperative mortality
Time frame: Day of surgery to 90-days after surgery
Incidence of liver insufficiency
Time frame: Day of surgery to 90-days after surgery
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Apr 2024.
- Derived from this study: PubMed 38580363Behman 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paul Karanicolas, MD, PhD principal investigator
Sunnybrook Health Sciences Centre
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active A, Active B and Lipid bolus in people with Hepatopancreaticobiliary (HPB) Malignancy and Surgery, run by Sunnybrook Health Sciences Centre at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 3 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Natural killer (NK) cell killing (time frame: Post-operative day 1 (Day 1) as compared to baseline (pre-operative)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04549662, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Apr 2024.