Immune-modulation Effects of an Arginine Rich Nutritional Supplement in Surgical Patients

A Randomized, Controlled Study Evaluating the Immune-Modulatory Effects of Perioperative Administration of Arginine Rich Nutritional Supplements With Mass Cytometry in Patient Undergoing Surgery

The primary objective of this study is to characterize the immune-modulatory effects of arginine-rich nutritional supplements in patients undergoing surgery. Numerical and functional changes of all circulating immune cells will be assessed with mass cytometry.

Study Overview

• Status: Completed
• Conditions: Immunity
• Intervention / Treatment: Dietary supplement: An arginine rich nutritional supplement

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 84305
      • Stanford University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Colon surgery for cancer
2. Patients ≥ 18 and ≤65 years of age
3. Patients willing and able to sign an informed consent form and Health Insurance and Portability Act (HIPAA) authorization and to comply with study procedures

Exclusion Criteria:

1. Patients on immune-suppressant therapy within the last 6 months (e.g. azathioprine or cyclosporine)
2. Patients pretreated (6 months) or currently on chemotherapy for cancer
3. Patients on radiation therapy (within 6 months)
4. Patients on chronic medication with potential immune-modulatory effects (e.g. daily oral morphine-equivalent intake > 30 mg)
5. Patients with metastatic disease
6. Patients with active infectious disease (within 2 months)
7. Patients with significant metabolic disease (e.g. diabetes type I)
8. Patients with clinically significant organ dysfunction including renal and hepatic dysfunction
9. Patients with significant cardiovascular and respiratory comorbidities resulting in impaired function and frailty
10. Patients with autoimmune disease (e.g. lupus)
11. Patients with Hx of substance abuse (e.g., alcoholism, drug dependency)
12. Undernourished patients as indicated by a weight loss >10% during the last 6 months
13. Patients with galactosemia
14. Patients who had undergone previous major abdominal surgery
15. Participation in another clinical trial of an investigational drug or device within the last 30 days prior to the first day of study that, in the investigator's opinion, would create increased risk to the participant or compromise the integrity or either study
16. Pregnancy
17. Other conditions compromising a participant's safety or the integrity of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Arginine rich nutritional supplement; 237 ml of an arginine rich nutritional supplement 4 times a day for the five days preceding surgery.	Dietary supplement: An arginine rich nutritional supplement; Impact is a nutritional supplement formulated with 18 grams of protein per serving and 24 essential nutrients including arginine.; Other Names: 'Impact' made by Nestle Corporation
No Intervention: No nutritional supplement; No specific nutritional requirements have to be met in this group.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in fractional representation of myeloid-derived suppressor cells (MDSC) from baseline.	The fraction of MDSCs will be quantified.	Base line (prior to 1st administration of arginine supplement), immediately prior to surgery, 24 hours, 72 hours and 120 hours after surgery.
Functional status change of myeloid-derived suppressor cells (MDSC) from baseline.	Intracellular phosphorylation events in MDSCs will be quantified.	Base line (prior to 1st administration of arginine supplement), immediately prior to surgery, 24 hours, 72 hours and 120 hours after surgery.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Impact of surgery on clinical recovery using multiple clinical measures and a validated questionnaire.	Outcome measures include the 1) Surgical Recovery Scale, 2) Pain (11-point numerical pain rating scale), 3) Consumption of analgesic drugs.	Daily for duration of hospital stay, then every 3 days trough postoperative week 5.

Other Outcome Measures

Outcome Measure	Time Frame
Fractional and absolute expansion/contraction of cluster of differentiation 4 (CD4)+ and cluster of differentiation 8 (CD8)+ cells	Base line (prior to 1st administration of arginine supplement), immediately prior to surgery, 24 hours, 72 hours and 120 hours after surgery.
Functional status of cluster of differentiation 4 (CD4)+ and cluster of differentiation 8 (CD8)+ cells	Base line (prior to 1st administration of arginine supplement), immediately prior to surgery, 24 hours, 72 hours and 120 hours after surgery.
Functional potency of cluster of differentiation 4 (CD4)+ and cluster of differentiation 8 (CD8)+ cells	Base line (prior to 1st administration of arginine supplement), immediately prior to surgery, 24 hours, 72 hours and 120 hours after surgery.
Capacity of cluster of differentiation 4 (CD4)+ and cluster of differentiation 8 (CD8)+ cells	Base line (prior to 1st administration of arginine supplement), immediately prior to surgery, 24 hours, 72 hours and 120 hours after surgery.

Collaborators and Investigators

• Sponsor: Martin Angst
• Investigators: Principal Investigator: Martin S Angst, MD, Stanford University SOM

Study record dates

Study Major Dates

• Study Start: July 1, 2013
• Primary Completion (Actual): June 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: June 18, 2013
• First Submitted That Met QC Criteria: June 20, 2013
• First Posted (Estimate): June 25, 2013

Study Record Updates

• Last Update Posted (Estimate): November 6, 2016
• Last Update Submitted That Met QC Criteria: November 4, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Other Study ID Numbers: 27485