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
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 45
- 试验地点
- 4
- 主要终点
- Natural killer (NK) cell killing
研究概览
简要总结
This is a randomized controlled blinded superiority trial to evaluate the impact of perioperative immunosupplementation on immune function following resection for hepatopancreaticobiliary (HPB) malignancy.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
结局指标
主要结局
Natural killer (NK) cell killing
时间窗: 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).
次要结局
- Secondary immune function outcomes: Immune cell subsets(Day of surgery to 30-days after surgery)
- Incidence of liver insufficiency(Day of surgery to 90-days after surgery)
- Length of stay(Day of surgery to day of discharge after surgery, assessed until day of discharge after surgery occurs)
- Secondary immune function outcomes: NK cell activating and inhibitory receptors(Day of surgery to 30-days after surgery)
- 90-day postoperative complications (Clavien-Dindo 3-5)(Day of surgery to 90-days after surgery)
- 90-day postoperative mortality(Day of surgery to 90-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)