Short Bowel SyndromePhase 2NCT00793195
Can SMOFlipid®, A Composite Parenteral Nutrition Lipid Emulsion, Prevent Progression Of Parenteral Nutrition Associated Liver Disease In Infants?
A Phase 2 study testing Intralipid 20% and SMOFlipid 20% in people with Short Bowel Syndrome and Intestinal Failure, run by The Hospital for Sick Children at 5 sites in Canada.
Trial summary
The aim of this study is to determine the feasibility of conducting a trial to examine the efficacy of an ω3FA (Omega-3 fatty acid) containing balanced lipid emulsion in the prevention of progression of PNALD in infants with Intestinal Failure/Short Bowel Syndrome (SBS) and early liver dysfunction. Read more about this study
- Who is it for?
- Ages Up to 24 months
- Conditions the study is for
- Short Bowel Syndrome, Intestinal Failure, Gastrointestinal Motility Disorder
- What is being tested?
- Intralipid 20% and SMOFlipid 20%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 5 sitesCanada
- Study dates
- Jan 2009to Jan 2012
- Phase
- Phase 2
- 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 Up to 24 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- ≤ 24 months of age at enrollment
- Evidence of early hepatic dysfunction
- Serum conjugated bilirubin ≥ 17 umol/L on 2 consecutive readings 7 days apart
- No evidence of sepsis
- Normal Temperature (T between 35.5C and 38.0C)
- Normal leukocyte count
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- Normal platelet count
- No systemic septic symptoms
- No prior administration of Omegaven
- ≥ 40% of total calories administered by PN
- Meet one of the following diagnostic categories
- Short Bowel Syndrome
- Abdominal surgical procedure including gastroschisis closure by any means and percutaneous drainage procedures within the past 6 months and has been receiving PN since surgery
- Intestinal Failure
- One of the following diagnoses for which the child is dependent on PN
- Gastrointestinal Motility Disorder
- Mucosal Enteropathy
- Expectation of the treating physician that the patient will require PN for at least 3 weeks following enrollment.
- Parents willing to participate including randomization
Who cannot join
- Sepsis or Hemodynamic Instability of any cause.
- Coagulopathy (Platelets ≤ 150 000, or INR ≥ 1.4)
- Hypersensitivity to fish-, egg- or soy protein or to any of the active substances or excipients
- Current enrollment in another clinical trial involving a surgical or pharmacologic intervention
- Serum conjugated bilirubin > 50 umol/L
- Hyperlipidaemia (any of)
Show all 26Show fewer
- LDL ≥ 4 mmol/L
- HDL ≥ 2 mmol/L
- Total cholesterol ≥ 5 mmol/L
- Triglycerides ≥ 1.5 mmol/L
- Treatment with intravenous N-Acetylcysteine or Ursodeoxycholic acid
- Renal insufficiency
- Creatinine ≥ 80 umol/L
- Disorders of Fluid Balance (any of)
- Serum Sodium < 130 mmol/L
- Serum Sodium > 145 mmol/L
- Unstable conditions
- Acute pulmonary edema
- Decompensated cardiac insufficiency
- Severe post-traumatic conditions
- Uncompensated diabetes mellitus
- Acute myocardial infarction
- Stroke within 3 months
- Thromboembolic event within 3 months
- Metabolic acidosis
- Serum Bicarbonate < 17 mmol/L
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Canada5 sites
Alberta Children's Hospital
Calgary, Alberta
Foothills Medical Center
Calgary, Alberta
Stollery Children's Hospital
Edmonton, Alberta
Hamilton Health Sciences
Hamilton, Ontario, L8N 3Z5
The Hospital for Sick Children
Toronto, Ontario
About this study
Official title: Can SMOFlipid®, A Composite Parenteral Nutrition Lipid Emulsion, Prevent Progression Of Parenteral Nutrition Associated Liver Disease In Infants? A Pilot Double Blind Randomized Controlled Trial
The aim of this study is to determine the feasibility of conducting a trial to examine the efficacy of an ω3FA (Omega-3 fatty acid) containing balanced lipid emulsion in the prevention of progression of PNALD in infants with Intestinal Failure/Short Bowel Syndrome (SBS) and early liver dysfunction.
Read the detailed description
Parenteral nutrition (PN) associated liver disease (PNALD), remains the primary cause of morbidity and mortality in infants with Short Bowel Syndrome (SBS) and intestinal failure. Although, the etiology is likely multi-factorial, lipids within parenteral nutrition solution have been implicated in its development. The standard lipid used in PN is typically, a soy based lipid (eg: Intralipid® - Fresenius Kabi) that primarily contains omega-6 fatty acids (ω6FAs). Animal and human studies have suggested that addition of omega-3 fatty acids (ω3FAs) to parenteral nutrition may decrease the incidence of hepatic injury, as well as have beneficial immunologic effects. SMOFlipid® (Fresenius Kabi) is a composite lipid emulsion, which contains polyunsaturated ω3 and ω6FAs, monounsaturated FAs, as well as medium chain FAs as integral constituents. All components (Soy-bean oil, medium chain triglycerides, olive oil, fish oil) have been used in humans, and the drug is approved for use in children in Europe. Based on its composition, we believe that this lipid preparation has the potential to prevent progression of liver disease in infants with SBS who are demonstrating evidence of liver dysfunction.
- Conditions
- Short Bowel Syndrome, Intestinal Failure, Gastrointestinal Motility Disorder, Mucosal Enteropathy
- Being tested
- Intralipid 20%, SMOFlipid 20%
- Keywords
- Neonates, Short Bowel Syndrome, Intestinal Failure, Liver Failure, Parenteral Nutrition, Intralipid, SMOF
- Medical subject headings
- Short Bowel Syndrome, Intestinal Failure, Liver Failure, Hyperphagia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intralipid 20%Drug
Dosing will be formulated according to a Nomogram for Parenteral Nutrition (PN) composition, which takes into account the percentage of the subject's caloric intake consumed parenterally. PN solution will be infused continuously over 12-24 hours by infusion pump, and the duration each day will depend on the enteral tolerance of the child. PN shall not be discontinued, unless the patient is taking 95% of calories enterally with good growth as evidence by appropriate weight gain. Subjects will receive the trial lipid for a total duration of 12 weeks or if they develop a serum conjugated bilirubin (sustained for 7 days) of 100 umol/l (6mg/dl) or full enteral tolerance prior to this end-point. Once the trial lipid is discontinued, in the event that PN is continued, subjects will return to the standard lipid preparation. A final follow-up data-point will be collected 4 weeks after the trial lipid is stopped.
SMOFlipid 20%Drug
Dosing will be formulated according to a Nomogram for Parenteral Nutrition (PN) composition, which takes into account the percentage of the subject's caloric intake consumed parenterally. PN solution will be infused continuously over 12-24 hours by infusion pump, and the duration each day will depend on the enteral tolerance of the child. PN shall not be discontinued, unless the patient is taking 95% of calories enterally with good growth as evidence by appropriate weight gain. Subjects will receive the trial lipid for a total duration of 12 weeks or if they develop a serum conjugated bilirubin (sustained for 7 days) of 100 umol/l (6mg/dl) or full enteral tolerance prior to this end-point. Once the trial lipid is discontinued, in the event that PN is continued, subjects will return to the standard lipid preparation. A final follow-up data-point will be collected 4 weeks after the trial lipid is stopped.
| Study group | Role | What they receive |
|---|---|---|
| 1) Intralipid | Active comparator | Fat Emulsions for Intravenous Nutrition Receives: Drug: Intralipid 20% |
| 2) SMOFlipid | Experimental | Fat Emulsions for Intravenous Nutrition Receives: Drug: SMOFlipid 20% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean serum conjugated bilirubin (umol/L)
Measured: 12 weeks
Secondary outcomes (7)
Proportion with the development of cholestasis (sustained serum conjugated bilirubin >50 umol/L for greater than 2 weeks in absence of sepsis)
Measured: 12 and 16 weeks
Proportion with progression of liver disease (sustained serum conjugated bilirubin >100 umol/L in absence of sepsis)
Measured: 12 and 16 weeks
Degree of enteral tolerance (%)
Measured: 12 and 16 weeks
Growth parameters
Measured: 12 and 16 weeks
Biochemical outcomes shall assess mean levels of "hepatic markers" (AST, ALT, ALP, GGT), coagulation parameters (PT, PTT, INR, platelets), serum lipid levels (triglycerides and cholesterol), serum albumin, and Nephelometry (lipid clearance).
Measured: 12 and 16 weeks
Immunologic outcomes shall include assessment of RBC phospholipids composition, C-reactive Protein (CRP) and serum immunologic marker (IL-1b, IL-2R, IL-6, IL-8, IL-10, TNF-α) assessment
Measured: 12 and 16 weeks
Feasibility of trial (recruitment, protocol adherence, estimated effect size
Measured: 4, 12 and 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Nov 2008 (estimated)
- Study startJan 2009
- Primary completionSep 2011
- Study completionJan 2012 (estimated)
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 Short Bowel SyndromeStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- Fresenius Kabi
- Investigators
- Paul Wales, Principal investigator, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00793195
- Sponsor's protocol ID
- 1000012566
- Status last verified
- Nov 2011
- First submitted
- 18 Nov 2008
- Last updated
- 3 Nov 2011
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Diamond IR, Grant RC, Pencharz PB, de Silva N, Feldman BM, Fitzgerald P, Sigalet D, Dicken B, Turner J, Marchand V, Ling SC, Moore AM, Avitzur Y, Wales PW. Preventing the Progression of Intestinal Failure-Associated Liver Disease in Infants Using a Composite Lipid Emulsion: A Pilot Randomized Controlled Trial of SMOFlipid. JPEN J Parenter Enteral Nutr. 2017 Jul;41(5):866-877. doi: 10.1177/0148607115626921. Epub 2016 Feb 2.
PubMed 26838529
Study at a glance
From the registry record, last updated by the sponsor on 3 Nov 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Can SMOFlipid®, A Composite Parenteral Nutrition Lipid Emulsion, Prevent Progression Of Parenteral Nutrition Associated Liver Disease In Infants? A Pilot Double Blind Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT00793195
- Acronym / sponsor ID
- 1000012566
- Conditions
- Short Bowel Syndrome, Intestinal Failure, Gastrointestinal Motility Disorder, Mucosal Enteropathy
- Keywords
- Neonates, Short Bowel Syndrome, Intestinal Failure, Liver Failure, Parenteral Nutrition, Intralipid, SMOF
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- Fresenius Kabi
- Study start
- Jan 2009
- Primary completion
- Sep 2011 (actual)
- Study completion
- Jan 2012 (estimated)
- First posted
- 19 Nov 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.
The aim of this study is to determine the feasibility of conducting a trial to examine the efficacy of an ω3FA (Omega-3 fatty acid) containing balanced lipid emulsion in the prevention of progression of PNALD in infants with Intestinal Failure/Short Bowel Syndrome (SBS) and early liver dysfunction.
Detailed description
Parenteral nutrition (PN) associated liver disease (PNALD), remains the primary cause of morbidity and mortality in infants with Short Bowel Syndrome (SBS) and intestinal failure. Although, the etiology is likely multi-factorial, lipids within parenteral nutrition solution have been implicated in its development. The standard lipid used in PN is typically, a soy based lipid (eg: Intralipid® - Fresenius Kabi) that primarily contains omega-6 fatty acids (ω6FAs). Animal and human studies have suggested that addition of omega-3 fatty acids (ω3FAs) to parenteral nutrition may decrease the incidence of hepatic injury, as well as have beneficial immunologic effects. SMOFlipid® (Fresenius Kabi) is a composite lipid emulsion, which contains polyunsaturated ω3 and ω6FAs, monounsaturated FAs, as well as medium chain FAs as integral constituents. All components (Soy-bean oil, medium chain triglycerides, olive oil, fish oil) have been used in humans, and the drug is approved for use in children in Europe. Based on its composition, we believe that this lipid preparation has the potential to prevent progression of liver disease in infants with SBS who are demonstrating evidence of liver dysfunction.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1) Intralipid | Active comparator | Drug: Intralipid 20%Fat Emulsions for Intravenous Nutrition |
| 2) SMOFlipid | Experimental | Drug: SMOFlipid 20%Fat Emulsions for Intravenous Nutrition |
Who may qualify
- Ages
- Up to 24 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (19 listed)
- ≤ 24 months of age at enrollment
- Evidence of early hepatic dysfunction
- ≥ 40% of total calories administered by PN
- Meet one of the following diagnostic categories
- Expectation of the treating physician that the patient will require PN for at least 3 weeks following enrollment.
Key exclusion criteria (26 listed)
- Sepsis or Hemodynamic Instability of any cause.
- Coagulopathy (Platelets ≤ 150 000, or INR ≥ 1.4)
- Hypersensitivity to fish-, egg- or soy protein or to any of the active substances or excipients
- Current enrollment in another clinical trial involving a surgical or pharmacologic intervention
- Serum conjugated bilirubin > 50 umol/L
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 |
|---|---|---|
| Intralipid 20%Dosing will be formulated according to a Nomogram for Parenteral Nutrition (PN) composition, which takes into account the percentage of the subject's caloric intake consumed parenterally. PN solution will be infused continuously over 12-24 hours by infusion pump, and the duration each day will depend on the enteral tolerance of the child. PN shall not be discontinued, unless the patient is taking 95% of calories enterally with good growth as evidence by appropriate weight gain. Subjects will receive the trial lipid for a total duration of 12 weeks or if they develop a serum conjugated bilirubin (sustained for 7 days) of 100 umol/l (6mg/dl) or full enteral tolerance prior to this end-point. Once the trial lipid is discontinued, in the event that PN is continued, subjects will return to the standard lipid preparation. A final follow-up data-point will be collected 4 weeks after the trial lipid is stopped. | Drug | 1) Intralipid |
| SMOFlipid 20%Dosing will be formulated according to a Nomogram for Parenteral Nutrition (PN) composition, which takes into account the percentage of the subject's caloric intake consumed parenterally. PN solution will be infused continuously over 12-24 hours by infusion pump, and the duration each day will depend on the enteral tolerance of the child. PN shall not be discontinued, unless the patient is taking 95% of calories enterally with good growth as evidence by appropriate weight gain. Subjects will receive the trial lipid for a total duration of 12 weeks or if they develop a serum conjugated bilirubin (sustained for 7 days) of 100 umol/l (6mg/dl) or full enteral tolerance prior to this end-point. Once the trial lipid is discontinued, in the event that PN is continued, subjects will return to the standard lipid preparation. A final follow-up data-point will be collected 4 weeks after the trial lipid is stopped. | Drug | 2) SMOFlipid |
Primary outcome
Mean serum conjugated bilirubin (umol/L)
Time frame: 12 weeks
7 secondary outcomes
Proportion with the development of cholestasis (sustained serum conjugated bilirubin >50 umol/L for greater than 2 weeks in absence of sepsis)
Time frame: 12 and 16 weeks
Proportion with progression of liver disease (sustained serum conjugated bilirubin >100 umol/L in absence of sepsis)
Time frame: 12 and 16 weeks
Degree of enteral tolerance (%)
Time frame: 12 and 16 weeks
Growth parameters
Time frame: 12 and 16 weeks
Biochemical outcomes shall assess mean levels of "hepatic markers" (AST, ALT, ALP, GGT), coagulation parameters (PT, PTT, INR, platelets), serum lipid levels (triglycerides and cholesterol), serum albumin, and Nephelometry (lipid clearance).
Time frame: 12 and 16 weeks
Immunologic outcomes shall include assessment of RBC phospholipids composition, C-reactive Protein (CRP) and serum immunologic marker (IL-1b, IL-2R, IL-6, IL-8, IL-10, TNF-α) assessment
Time frame: 12 and 16 weeks
Feasibility of trial (recruitment, protocol adherence, estimated effect size
Time frame: 4, 12 and 16 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Nov 2011.
- Derived from this study: PubMed 26838529Diamond IR, Grant RC, Pencharz PB, de Silva N, Feldman BM, Fitzgerald P, Sigalet D, Dicken B, Turner J, Marchand V, Ling SC, Moore AM, Avitzur Y, Wales PW. Preventing the Progression of Intestinal Failure-Associated Liver Disease in Infants Using a Composite Lipid Emulsion: A Pilot Randomized Controlled Trial of SMOFlipid. JPEN J Parenter Enteral Nutr. 2017 Jul;41(5):866-877. doi: 10.1177/0148607115626921. Epub 2016 Feb 2.
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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 Wales principal investigator
The Hospital for Sick Children
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Intralipid 20% and SMOFlipid 20% in people with Short Bowel Syndrome and Intestinal Failure, run by The Hospital for Sick Children at 5 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 19 inclusion and 26 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: status not confirmed, as of the sponsor's last update on 3 Nov 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
Mean serum conjugated bilirubin (umol/L) (time frame: 12 weeks). 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 NCT00793195, 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 Nov 2011.