Ignite Creation Date:
2024-05-05 @ 11:52 AM
Last Modification Date:
2024-10-26 @ 9:14 AM
Study NCT ID:
NCT00152945
Status:
COMPLETED
Last Update Posted:
2012-10-02
First Post:
2005-09-08
Brief Title:
Determining the Responsiveness of Intestinal Lipoprotein Production to an Elevation of Plasma Free Fatty Acids
Sponsor:
University Health Network Toronto
Organization:
University Health Network Toronto
Study Overview
Official Title:
None
Status:
COMPLETED
Status Verified Date:
2012-09
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Lipoproteins are large complexes of molecules that transport lipids primarily triglycerides and cholesterol through the blood The intestine has traditionally been viewed as a passive organ with respect to lipoprotein production with intestinal lipoprotein production rates responding mainly to fat ingestion and absorption The investigators have recently demonstrated in animal models that there is an overproduction of intestinal lipoproteins in both the fasted and the fed state The investigators have also recently demonstrated that an elevation of plasma free fatty acids FFAs stimulates intestinal lipoprotein in hamsters It is not known whether intestinal lipoprotein production can be acutely stimulated by an elevation of plasma FFAs in humans
Hypothesis Intestinal lipoprotein particle production in humans can be stimulated by an acute elevation of plasma free fatty acids
Hypothesis Intestinal lipoprotein particle production in humans can be stimulated by an acute elevation of plasma free fatty acids
Detailed Description:
This study proposes to use a published stable isotope method to study the kinetics of apoB48 and apoB100 in the constant fed state in healthy subjects These studies will be performed in 10 healthy lean men and women aged 18 to 65 years of age Each subject will serve as hisher own control and will undergo 3 separate lipoprotein turnover studies in random order 4 to 6 weeks apart Since the infusion of intralipid a synthetic triglyceride emulsion that provides a source of fatty acids and heparin to activate lipoprotein lipase raises both FFAs and glycerol two control studies will be performed one with saline and one with glycerol infusion ApoB48-containing lipoprotein particle production will be determined as outlined above but for this study in the fasted state in response to the following interventions
1 Intralipid 20 solution 40 mlhr and heparin 250 uhr infusion to achieve an 2-fold elevation of plasma FFAs as previously shown starting 90 minutes prior to and continuing throughout the lipoprotein turnover experiment
2 Saline infusion control study and
3 Glycerol control study in which glycerol will be infused at a rate of 225 ghr to simulate the infusion of glycerol contained in Intralipid
Stable isotope infusion protocol Following a 14-h overnight fast an IV will be inserted into a superficial vein in each forearm one for infusion and one for sampling At 7 am a fasting blood sample will be drawn and the subject will begin to ingest the first of 15 identical small hourly meals each equivalent to 115th of their daily food intake This will be achieved by giving the patient the drink BOOST Mead Johnson Nutritionals Ottawa On and using the Harris Benedict Equation HBE to determine the number of total energy requirements This is based on height weight age and activity factors The subject will have nothing else to eat until the end of the study At the same time an IV infusion with either heparin plus intralipid or saline or glycerol as indicated above will be started At 10 am 3 hours after starting the ingestion of hourly feeds a primed-constant infusion of deuterium-labeled leucine D3L-leucine 98 Cambridge Isotope Laboratories MA will be started as previously described 06 mgkg as an initial injection and then 06 mgkghr thereafter In addition an IV bolus of d5-glycerol 100 mmolkg will be administered These are standard techniques used for the assessment of lipoprotein metabolism in humans Leucine an amino acid and glycerol an intermediary metabolite are used by cells in the body as building blocks for proteins fats and for energy The form of leucine that will be administered is deuterated leucine chemical formula L-555-2H3 and the form of glycerol is d5-glycerol which has been enriched with the naturally occurring isotope chemical variant of hydrogen 2H Deuterated leucine and glycerol are stable isotopes that occur naturally in the environment and in the body and there are no healthsafety issues regarding the infusion of the amounts of deuterated leucine and glycerol indicated above The solutions are prepared using sterile techniques and are monitored for contamination prior to administration Blood samples will be collected prior to and at the following time points after administration of the stable isotopes 1hr 2hr 3hr 5hr 7hr 9hr 10hr 11hr and 12hr A total of 340 ml of blood will be drawn
1 Intralipid 20 solution 40 mlhr and heparin 250 uhr infusion to achieve an 2-fold elevation of plasma FFAs as previously shown starting 90 minutes prior to and continuing throughout the lipoprotein turnover experiment
2 Saline infusion control study and
3 Glycerol control study in which glycerol will be infused at a rate of 225 ghr to simulate the infusion of glycerol contained in Intralipid
Stable isotope infusion protocol Following a 14-h overnight fast an IV will be inserted into a superficial vein in each forearm one for infusion and one for sampling At 7 am a fasting blood sample will be drawn and the subject will begin to ingest the first of 15 identical small hourly meals each equivalent to 115th of their daily food intake This will be achieved by giving the patient the drink BOOST Mead Johnson Nutritionals Ottawa On and using the Harris Benedict Equation HBE to determine the number of total energy requirements This is based on height weight age and activity factors The subject will have nothing else to eat until the end of the study At the same time an IV infusion with either heparin plus intralipid or saline or glycerol as indicated above will be started At 10 am 3 hours after starting the ingestion of hourly feeds a primed-constant infusion of deuterium-labeled leucine D3L-leucine 98 Cambridge Isotope Laboratories MA will be started as previously described 06 mgkg as an initial injection and then 06 mgkghr thereafter In addition an IV bolus of d5-glycerol 100 mmolkg will be administered These are standard techniques used for the assessment of lipoprotein metabolism in humans Leucine an amino acid and glycerol an intermediary metabolite are used by cells in the body as building blocks for proteins fats and for energy The form of leucine that will be administered is deuterated leucine chemical formula L-555-2H3 and the form of glycerol is d5-glycerol which has been enriched with the naturally occurring isotope chemical variant of hydrogen 2H Deuterated leucine and glycerol are stable isotopes that occur naturally in the environment and in the body and there are no healthsafety issues regarding the infusion of the amounts of deuterated leucine and glycerol indicated above The solutions are prepared using sterile techniques and are monitored for contamination prior to administration Blood samples will be collected prior to and at the following time points after administration of the stable isotopes 1hr 2hr 3hr 5hr 7hr 9hr 10hr 11hr and 12hr A total of 340 ml of blood will be drawn
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| CIHR Grant 777509574 | None | None | None |