Postoperative Protein CatabolismNCT00614133
Effect of Intravenous Nutrition and Epidural Analgesia on Protein Loss After Surgery
A study testing Intravenous nutrition with glucose and amino acids and Intravenous nutrition with glucose and amino acids. in people with Postoperative Protein Catabolism, run by McGill University Health Centre/Research Institute of the McGill University Health Centre at 1 site in Canada.
Trial summary
Loss of muscle mass and body protein are the main causes of fatigue after bowel surgery, which may result in a longer hospital stay and a higher rate of complications. This particularly applies to malnourished patients with cancer who undergo surgery with less muscle protein reserves than patients who are… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Postoperative Protein Catabolism
- What is being tested?
- Intravenous nutrition with glucose and amino acids and Intravenous nutrition with glucose and amino acids.
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteCanada
- Study dates
- Jun 2004to Jun 2007
- 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
- American Society of Anesthesiologists <3
- colorectal surgery for non-metastatic colorectal carcinoma including right and left hemicolectomy, transverse, subtotal and total colectomy, sigmoid resection
- ability to give informed consent
Who cannot join
- signs of severe malnutrition or obesity: body mass index <18 or >25 >10% involuntary body weight loss over the preceding 6 months serum albumin <21 g/L
- significant cardiorespiratory, hepatic, renal and neurological disease
- ingestion of drugs known to affect protein, glucose and lipid metabolism (for example steroids)
- musculoskeletal or neuromuscular disease
- severe anemia (hemoglobin <10 g/dL)
- pregnancy
- history of severe sciatica or back surgery or other conditions which contraindicate the use of epidural catheters
Trial locations and contacts
1 site in 1 country.
Canada1 site
Royal Victoria Hospital, McGill University Health Centre
Montreal, Quebec, H3A 1A1
About this study
Official title: Hypocaloric Isonitrogenous Nutrition and Epidural Analgesia: a Novel Strategy to Induce Anabolism After Surgery
Loss of muscle mass and body protein are the main causes of fatigue after bowel surgery, which may result in a longer hospital stay and a higher rate of complications. This particularly applies to malnourished patients with cancer who undergo surgery with less muscle protein reserves than patients who are well-nourished. Anesthesiologists can favourably influence these undesirable consequences of surgery by choosing the type of pain treatment, i.e. analgesia. Our group recently observed that pain treatment with epidural catheters (these are placed in the so called epidural space, which lies between the spine and the skin of the back), in contrast to the more conventional use of intravenous morphine, can prevent the loss of body protein after surgery.
The goal of the present research program is to study whether this protein sparing effect of epidural analgesia can be further augmented if we feed our patients intravenously with glucose and protein starting the day prior to surgery. We believe that this new concept will not only avoid the increased protein loss after surgery, but will also help patients to build up new protein which is needed to fight the stress caused by the operation.
Read the detailed description
The major objective of the nutritional management of surgical patients is to accelerate wound healing and increase resistance to infection while preventing wastage of functional and structural proteins. Parenteral nutrition represents a useful strategy to achieve this goal, particularly in patients undergoing major abdominal procedures with temporary intolerance to oral feeding. At present administration of large, hypercaloric amounts of glucose together with amino acids is the only nutritional modality to establish a positive protein balance (anabolism) after surgery. The fact that hyperalimentation requires central venous cannulation, causes hyperglycemia and is associated with increased morbidity is an impediment to its routine use. Attempts to induce anabolism by diminishing the glucose load to iso- or hypocaloric quantities failed because of
- failure to control for type and quality of perioperative analgesia
- inadequate assessment of the patient's catabolic status prior to surgery with subsequent
- lack of individualization of energy and substrate supply.
We recently demonstrated that segmental pain relief by epidural analgesia facilitates oxidative glucose utilization thereby decreasing the amount of glucose necessary to attenuate protein losses after surgery. Hypocaloric glucose and epidural analgesia prevented the postoperative increase in protein oxidation, but only if preoperative fasting was avoided, i.e. the glucose infusion was started 24 hours before surgery. We also showed that patients with epidural analgesia could be rendered anabolic by short term administration of glucose and amino acids. Based on our findings of anti-catabolic and anabolic effects of epidural analgesia in the presence of energy and substrate supply we now propose that epidural analgesia and hypocaloric parenteral nutrition initiated 24 hours before colorectal surgery will produce a more positive postoperative protein balance including a greater muscle protein synthesis than when initiated with skin incision.
In order to test the validity of this assumption, patients scheduled for elective colorectal cancer surgery will be randomly assigned to an "early" or "late" feeding protocol. "Early" nutrition will start 24 hours prior to surgery, "late" nutrition will commence with surgical skin incision. Nutrition will be adjusted to provide 50% of the patient's actual energy expenditure as glucose and 20% as amino acids. The stable isotope tracer L-[1-13C]leucine will be applied to assess whole body protein breakdown, amino acid oxidation and protein synthesis. A positive protein balance (difference between protein synthesis and protein breakdown) will be used as an indicator of anabolism. Because whole body protein kinetics provide no insight into metabolic processes at organ level (muscle, liver), the fractional synthesis rates of albumin, fibrinogen and muscle protein will also be determined after surgery.
The demonstration of anabolic effects of epidural analgesia and nutrition with less than half the commonly used energy would have a valuable practical application. If the nutrient load can be decreased, use can be made of peripheral veins and hyperglycemia can be avoided, thus making nutritional therapy more efficacious, safer and available to more patients.
- Conditions
- Postoperative Protein Catabolism
- Being tested
- Intravenous nutrition with glucose and amino acids, Intravenous nutrition with glucose and amino acids.
- Keywords
- protein metabolism, surgery, parenteral nutrition
- Medical subject headings
- Hyperphagia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous nutrition with glucose and amino acidsOther
Glucose and amino acids intravenously starting 20 hours before the operation until the second postoperative day. Glucose provides 50% and amino acids 20% of each patient's measured resting energy expenditure.
Intravenous nutrition with glucose and amino acids.Other
Glucose and amino acids intravenously starting with surgical skin incision until the second postoperative day. Glucose provides 50% and amino acids 20% of each patient's measured resting energy expenditure.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Preoperative nutrition. Receives: Other: Intravenous nutrition with glucose and amino acids |
| 2 | Active comparator | Preoperative fasting. Receives: Other: Intravenous nutrition with glucose and amino acids. |
What is being measured
The primary outcome is the main question the study is designed to answer.
protein balance
Measured: two days after surgery
Secondary outcomes (1)
albumin synthesis, fibrinogen synthesis, total plasma protein synthesis, mRNA expression of ubiquitin
Measured: two 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 posted13 Feb 2008 (estimated)
- Study startJun 2004
- Primary completionJun 2007
- Study completionJun 2007
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 Postoperative Protein CatabolismStudies of the same condition, open and under way.
- More trials run by McGill University Health Centre/Research Institute of the McGill University Health 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
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- McGill University Health Centre/Research Institute of the McGill University Health Centre
- Sponsor type
- University, hospital or other
- Investigators
- Thomas P Schricker, MD PhD, Principal investigator, Department of Anaesthesia, McGill University Health Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00614133
- Sponsor's protocol ID
- MOP-64456
- Status last verified
- Jan 2008
- First submitted
- 30 Jan 2008
- Last updated
- 13 Feb 2008
- Results posted
- No
- Data monitoring committee
- No
Publications
Schricker T, Meterissian S, Lattermann R, Adegoke OA, Marliss EB, Mazza L, Eberhart L, Carli F, Nitschman E, Wykes L. Anticatabolic effects of avoiding preoperative fasting by intravenous hypocaloric nutrition: a randomized clinical trial. Ann Surg. 2008 Dec;248(6):1051-9. doi: 10.1097/SLA.0b013e31818842d8.
PubMed 19092350
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Hypocaloric Isonitrogenous Nutrition and Epidural Analgesia: a Novel Strategy to Induce Anabolism After Surgery
- ClinicalTrials.gov ID
- NCT00614133
- Acronym / sponsor ID
- MOP-64456
- Conditions
- Postoperative Protein Catabolism
- Keywords
- protein metabolism, surgery, parenteral nutrition
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 22 participants (actual)
- Lead sponsor
- McGill University Health Centre/Research Institute of the McGill University Health CentreUniversity, hospital or other
- Study start
- Jun 2004
- Primary completion
- Jun 2007 (actual)
- Study completion
- Jun 2007 (actual)
- First posted
- 13 Feb 2008 (estimated)
- 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.
Loss of muscle mass and body protein are the main causes of fatigue after bowel surgery, which may result in a longer hospital stay and a higher rate of complications. This particularly applies to malnourished patients with cancer who undergo surgery with less muscle protein reserves than patients who are well-nourished. Anesthesiologists can favourably influence these undesirable consequences of surgery by choosing the type of pain treatment, i.e. analgesia. Our group recently observed that pain treatment with epidural catheters (these are placed in the so called epidural space, which lies between the spine and the skin of the back), in contrast to the more conventional use of intravenous morphine, can prevent the loss of body protein after surgery.
The goal of the present research program is to study whether this protein sparing effect of epidural analgesia can be further augmented if we feed our patients intravenously with glucose and protein starting the day prior to surgery. We believe that this new concept will not only avoid the increased protein loss after surgery, but will also help patients to build up new protein which is needed to fight the stress caused by the operation.
Detailed description
The major objective of the nutritional management of surgical patients is to accelerate wound healing and increase resistance to infection while preventing wastage of functional and structural proteins. Parenteral nutrition represents a useful strategy to achieve this goal, particularly in patients undergoing major abdominal procedures with temporary intolerance to oral feeding. At present administration of large, hypercaloric amounts of glucose together with amino acids is the only nutritional modality to establish a positive protein balance (anabolism) after surgery. The fact that hyperalimentation requires central venous cannulation, causes hyperglycemia and is associated with increased morbidity is an impediment to its routine use. Attempts to induce anabolism by diminishing the glucose load to iso- or hypocaloric quantities failed because of
- failure to control for type and quality of perioperative analgesia
- inadequate assessment of the patient's catabolic status prior to surgery with subsequent
- lack of individualization of energy and substrate supply.
We recently demonstrated that segmental pain relief by epidural analgesia facilitates oxidative glucose utilization thereby decreasing the amount of glucose necessary to attenuate protein losses after surgery. Hypocaloric glucose and epidural analgesia prevented the postoperative increase in protein oxidation, but only if preoperative fasting was avoided, i.e. the glucose infusion was started 24 hours before surgery. We also showed that patients with epidural analgesia could be rendered anabolic by short term administration of glucose and amino acids. Based on our findings of anti-catabolic and anabolic effects of epidural analgesia in the presence of energy and substrate supply we now propose that epidural analgesia and hypocaloric parenteral nutrition initiated 24 hours before colorectal surgery will produce a more positive postoperative protein balance including a greater muscle protein synthesis than when initiated with skin incision.
In order to test the validity of this assumption, patients scheduled for elective colorectal cancer surgery will be randomly assigned to an "early" or "late" feeding protocol. "Early" nutrition will start 24 hours prior to surgery, "late" nutrition will commence with surgical skin incision. Nutrition will be adjusted to provide 50% of the patient's actual energy expenditure as glucose and 20% as amino acids. The stable isotope tracer L-[1-13C]leucine will be applied to assess whole body protein breakdown, amino acid oxidation and protein synthesis. A positive protein balance (difference between protein synthesis and protein breakdown) will be used as an indicator of anabolism. Because whole body protein kinetics provide no insight into metabolic processes at organ level (muscle, liver), the fractional synthesis rates of albumin, fibrinogen and muscle protein will also be determined after surgery.
The demonstration of anabolic effects of epidural analgesia and nutrition with less than half the commonly used energy would have a valuable practical application. If the nutrient load can be decreased, use can be made of peripheral veins and hyperglycemia can be avoided, thus making nutritional therapy more efficacious, safer and available to more patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Other: Intravenous nutrition with glucose and amino acidsPreoperative nutrition. |
| 2 | Active comparator | Other: Intravenous nutrition with glucose and amino acids.Preoperative fasting. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- American Society of Anesthesiologists <3
- colorectal surgery for non-metastatic colorectal carcinoma including right and left hemicolectomy, transverse, subtotal and total colectomy, sigmoid resection
- ability to give informed consent
Key exclusion criteria (7 listed)
- signs of severe malnutrition or obesity: body mass index <18 or >25 >10% involuntary body weight loss over the preceding 6 months serum albumin <21 g/L
- significant cardiorespiratory, hepatic, renal and neurological disease
- ingestion of drugs known to affect protein, glucose and lipid metabolism (for example steroids)
- musculoskeletal or neuromuscular disease
- severe anemia (hemoglobin <10 g/dL)
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 |
|---|---|---|
| Intravenous nutrition with glucose and amino acidsGlucose and amino acids intravenously starting 20 hours before the operation until the second postoperative day. Glucose provides 50% and amino acids 20% of each patient's measured resting energy expenditure. | Other | 1 |
| Intravenous nutrition with glucose and amino acids.Glucose and amino acids intravenously starting with surgical skin incision until the second postoperative day. Glucose provides 50% and amino acids 20% of each patient's measured resting energy expenditure. | Other | 2 |
Primary outcome
protein balance
Time frame: two days after surgery
1 secondary outcome
albumin synthesis, fibrinogen synthesis, total plasma protein synthesis, mRNA expression of ubiquitin
Time frame: two 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 13 Feb 2008.
- Derived from this study: PubMed 19092350Schricker T, Meterissian S, Lattermann R, Adegoke OA, Marliss EB, Mazza L, Eberhart L, Carli F, Nitschman E, Wykes L. Anticatabolic effects of avoiding preoperative fasting by intravenous hypocaloric nutrition: a randomized clinical trial. Ann Surg. 2008 Dec;248(6):1051-9. doi: 10.1097/SLA.0b013e31818842d8.
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.
Thomas P Schricker, MD PhD principal investigator
Department of Anaesthesia, McGill University Health Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Intravenous nutrition with glucose and amino acids and Intravenous nutrition with glucose and amino acids. in people with Postoperative Protein Catabolism, run by McGill University Health Centre/Research Institute of the McGill University Health Centre at 1 site 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 3 inclusion and 7 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 13 Feb 2008. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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?
protein balance (time frame: two days after surgery). 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 NCT00614133, 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 13 Feb 2008.