AtherosclerosisNCT00005532
Dietary Fat, Plasma Lipids, and Other CHD Risk Factors
An observational study of Atherosclerosis and Cardiovascular Diseases, run by Tufts University.
Trial summary
To assess the extent to which consumption of different sources of hydrogenated fat relative to unhydrogenated oil or butter alters plasma lipoprotein concentrations and measures of lipid metabolism. Read more about this study
- Who is it for?
- Ages Up to 100 years, men only
- Conditions the study is for
- Atherosclerosis, Cardiovascular Diseases, Coronary Disease
- How many people
- Not given
- Where
- No sites listed yet
- Study dates
- May 1996to Aug 2005
- Phase
- Observational
- 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 100 years
- Men only
- No healthy volunteers
- Child, Adult, Older adult
No eligibility criteria
About this study
To assess the extent to which consumption of different sources of hydrogenated fat relative to unhydrogenated oil or butter alters plasma lipoprotein concentrations and measures of lipid metabolism.
Read the detailed description
BACKGROUND:
Although the consumption of trans-fatty acids or hydrogenated fat has consistently been shown to elevate concentrations of total and LDL cholesterol, the effects on HDL-c and Lp(a) are inconsistent, especially when the fats were consumed at moderate levels. In addition, little is known about the mechanisms by which trans-fatty acids increase total and LDL cholesterol levels or how they may alter the atherogenecity of lipoprotein subfractions. The study interventions employ commonly used hydrogenated fats with a wide range of trans-fatty acid levels (1.5-9.8 percent). The impact will be assessed within the guidelines currently recommended for individuals with moderately elevated plasma levels for which dietary modification is often the first approach to treatment. The results of the study may lead to improved public health recommendations concerning trans-fatty acid and hydrogenated fat intake.
DESIGN NARRATIVE:
Forty subjects (20 male, 20 female) ages 50 or older, with LDL cholesterol concentrations greater than 130 mg/dl were fed each of five diets for eight week periods. The baseline diet consisted of 36 percent of energy as fat (15 percent saturated, 15 percent monosaturated, 6 percent polyunsaturated) and 160 mg cholesterol/1000 kcal. The experimental diets contained 30 percent energy as fat, 2/3 of which was derived from each of the following: 1) unhydrogenated liquid soybean oil, 2) soybean oil margarine in tub form, 3) commercial shortening, and 4) butter in a randomized double blind, cross-over design. With the exception of the experimental fat, all other foods in the reduced fat diets were identical.
The study assessed the impact of consuming diets enriched in hydrogenated and other fats on a) plasma lipids and lipoprotein concentrations, b) apolipoproteins A-1 and B and Lp(a) concentrations, c) parameters related to HDL cholesterol [particle size, composition, subfraction distribution (HDL2 and HDL3, and HDL with and without A-II)], d) susceptibility of LDL to oxidation, e) activities of lecithin cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein, and f) rates of endogenous cholesterol synthesis.
The study was renewed in FY 2000 is to assess the impact of newer approaches to dietary modification with the intent of reducing the risk of developing cardiovascular disease. The specific aims of the study are as follow: 1) to assess the impact of substituting two classes of fats specifically formulated to substitute for hydrogenated fats (i.e., trans-free margarines and genetically modified/selectively bred oils) on serum lipid levels (total, VLDL, LDL, HDL, HDL2 and HDL3 cholesterol; triglyceride; apo A-l and B; Lp[a]), immune function, and prostaglandin levels, and 2) to address unresolved issues related to plant sterols, including the relative efficacy of currently available preparations, impact of the fat and cholesterol content of the diet, and effect of dosing frequency on serum lipids, endogenous cholesterol synthesis, cholesterol absorption, and fat soluble vitamin levels. Study subjects are older (50-75 y) hypercholesterolemic female and male subjects (LDL cholesterol 130-160 mg/dl). Each 5-week diet phase will be scheduled in randomized order; all food and drink will be provided. In Part 1, Study 1, subjects will consume each of 3 diets (30 percent fat [2/3 experimental fat], 80 mg cholesterol/1000 kcal) with the following experimental fats: conventional soft margarine; trans-free margarine (interesterified palm kernel + liquid oil); trans-free margarine (fully hydrogenated soybean oil + liquid oil). In Part 1, Study 2, subjects will consume each of 6 diets (as above) with the following experimental fats: hydrogenated soybean (shortening), high oleic sunflower, high oleic soybean, high oleic canola, low saturated soybean and low linolenic soybean oils. In Part 2, Study 1, subjects will consume each of 4 diets (38 percent fat [15 percent SFA, 14 percent MUFA, 6 percent PUFA], 200 mg cholesterol/1000 kcal), baseline and the following: sitostanol ester; sitostenol ester, and genetically modified high sterol oil. In Part 2, Study 2, subjects will consume each of 4 plant sterol enriched diets, high fat (as above) with high (200 mg) or low (80 mg) cholesterol/1000 kcal, and low fat (20 percent fat [5 percent SFA, 7.5 percent MUFA, 7.5 percent PUFA]) with high or low cholesterol. In Part 2, Study 3, the effect of dosing regime will be assessed using the most efficacious plant sterol as identified in Study 1 and diet as in Study 2 (single bolus or in 3 divided doses).
- Medical subject headings
- Atherosclerosis, Cardiovascular Diseases, Coronary Disease, Heart Diseases
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2000 (estimated)
- Study startMay 1996
- Study completionAug 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for AtherosclerosisStudies of the same condition, open and under way.
- 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
- Observational
Sponsor and investigators
- Lead sponsor
- Tufts University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Investigators
- Alice Lichtenstein, Tufts University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00005532
- Sponsor's protocol ID
- 5065
- Other IDs
- R01HL054727
- Status last verified
- Jan 2016
- First submitted
- 25 May 2000
- Last updated
- 8 Jan 2016
- Results posted
- No
Publications
Schwab US, Ausman LM, Vogel S, Li Z, Lammi-Keefe CJ, Goldin BR, Ordovas JM, Schaefer EJ, Lichtenstein AH. Dietary cholesterol increases the susceptibility of low density lipoprotein to oxidative modification. Atherosclerosis. 2000 Mar;149(1):83-90. doi: 10.1016/s0021-9150(99)00310-x.
PubMed 10704618Matthan NR, Raeini-Sarjaz M, Lichtenstein AH, Ausman LM, Jones PJ. Deuterium uptake and plasma cholesterol precursor levels correspond as methods for measurement of endogenous cholesterol synthesis in hypercholesterolemic women. Lipids. 2000 Sep;35(9):1037-44. doi: 10.1007/s11745-000-0616-9.
PubMed 11026626Matthan NR, Cianflone K, Lichtenstein AH, Ausman LM, Jauhiainen M, Jones PJ. Hydrogenated fat consumption affects acylation-stimulating protein levels and cholesterol esterification rates in moderately hypercholesterolemic women. J Lipid Res. 2001 Nov;42(11):1841-8.
PubMed 11714853Lichtenstein AH, Jauhiainen M, McGladdery S, Ausman LM, Jalbert SM, Vilella-Bach M, Ehnholm C, Frohlich J, Schaefer EJ. Impact of hydrogenated fat on high density lipoprotein subfractions and metabolism. J Lipid Res. 2001 Apr;42(4):597-604.
PubMed 11290832Lichtenstein AH, Ausman LM, Jalbert SM, Schaefer EJ. Effects of different forms of dietary hydrogenated fats on serum lipoprotein cholesterol levels. N Engl J Med. 1999 Jun 24;340(25):1933-40. doi: 10.1056/NEJM199906243402501.
PubMed 10379016Han SN, Leka LS, Lichtenstein AH, Ausman LM, Schaefer EJ, Meydani SN. Effect of hydrogenated and saturated, relative to polyunsaturated, fat on immune and inflammatory responses of adults with moderate hypercholesterolemia. J Lipid Res. 2002 Mar;43(3):445-52.
PubMed 11893781Lichtenstein AH, Ausman LM, Jalbert SM, Vilella-Bach M, Jauhiainen M, McGladdery S, Erkkila AT, Ehnholm C, Frohlich J, Schaefer EJ. Efficacy of a Therapeutic Lifestyle Change/Step 2 diet in moderately hypercholesterolemic middle-aged and elderly female and male subjects. J Lipid Res. 2002 Feb;43(2):264-73.
PubMed 11861668Lichtenstein AH, Erkkila AT, Lamarche B, Schwab US, Jalbert SM, Ausman LM. Influence of hydrogenated fat and butter on CVD risk factors: remnant-like particles, glucose and insulin, blood pressure and C-reactive protein. Atherosclerosis. 2003 Nov;171(1):97-107. doi: 10.1016/j.atherosclerosis.2003.07.005.
PubMed 14642411Mauger JF, Lichtenstein AH, Ausman LM, Jalbert SM, Jauhiainen M, Ehnholm C, Lamarche B. Effect of different forms of dietary hydrogenated fats on LDL particle size. Am J Clin Nutr. 2003 Sep;78(3):370-5. doi: 10.1093/ajcn/78.3.370.
PubMed 12936917Matthan NR, Welty FK, Barrett PH, Harausz C, Dolnikowski GG, Parks JS, Eckel RH, Schaefer EJ, Lichtenstein AH. Dietary hydrogenated fat increases high-density lipoprotein apoA-I catabolism and decreases low-density lipoprotein apoB-100 catabolism in hypercholesterolemic women. Arterioscler Thromb Vasc Biol. 2004 Jun;24(6):1092-7. doi: 10.1161/01.ATV.0000128410.23161.be. Epub 2004 Apr 15.
PubMed 15087307Gordon LB, Harten IA, Patti ME, Lichtenstein AH. Reduced adiponectin and HDL cholesterol without elevated C-reactive protein: clues to the biology of premature atherosclerosis in Hutchinson-Gilford Progeria Syndrome. J Pediatr. 2005 Mar;146(3):336-41. doi: 10.1016/j.jpeds.2004.10.064.
PubMed 15756215Matthan NR, Jalbert SM, Lamon-Fava S, Dolnikowski GG, Welty FK, Barrett HR, Schaefer EJ, Lichtenstein AH. TRL, IDL, and LDL apolipoprotein B-100 and HDL apolipoprotein A-I kinetics as a function of age and menopausal status. Arterioscler Thromb Vasc Biol. 2005 Aug;25(8):1691-6. doi: 10.1161/01.ATV.0000172629.12846.b8. Epub 2005 Jun 2.
PubMed 15933247
Study at a glance
From the registry record, last updated by the sponsor on 8 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dietary Fat, Plasma Lipids, and Other CHD Risk Factors
- ClinicalTrials.gov ID
- NCT00005532
- Acronym / sponsor ID
- 5065
- Study type
- Observational
- Recruitment status
- Completed
- Lead sponsor
- Tufts UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- May 1996
- Study completion
- Aug 2005
- First posted
- 26 May 2000 (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.
To assess the extent to which consumption of different sources of hydrogenated fat relative to unhydrogenated oil or butter alters plasma lipoprotein concentrations and measures of lipid metabolism.
Detailed description
BACKGROUND:
Although the consumption of trans-fatty acids or hydrogenated fat has consistently been shown to elevate concentrations of total and LDL cholesterol, the effects on HDL-c and Lp(a) are inconsistent, especially when the fats were consumed at moderate levels. In addition, little is known about the mechanisms by which trans-fatty acids increase total and LDL cholesterol levels or how they may alter the atherogenecity of lipoprotein subfractions. The study interventions employ commonly used hydrogenated fats with a wide range of trans-fatty acid levels (1.5-9.8 percent). The impact will be assessed within the guidelines currently recommended for individuals with moderately elevated plasma levels for which dietary modification is often the first approach to treatment. The results of the study may lead to improved public health recommendations concerning trans-fatty acid and hydrogenated fat intake.
DESIGN NARRATIVE:
Forty subjects (20 male, 20 female) ages 50 or older, with LDL cholesterol concentrations greater than 130 mg/dl were fed each of five diets for eight week periods. The baseline diet consisted of 36 percent of energy as fat (15 percent saturated, 15 percent monosaturated, 6 percent polyunsaturated) and 160 mg cholesterol/1000 kcal. The experimental diets contained 30 percent energy as fat, 2/3 of which was derived from each of the following: 1) unhydrogenated liquid soybean oil, 2) soybean oil margarine in tub form, 3) commercial shortening, and 4) butter in a randomized double blind, cross-over design. With the exception of the experimental fat, all other foods in the reduced fat diets were identical.
The study assessed the impact of consuming diets enriched in hydrogenated and other fats on a) plasma lipids and lipoprotein concentrations, b) apolipoproteins A-1 and B and Lp(a) concentrations, c) parameters related to HDL cholesterol [particle size, composition, subfraction distribution (HDL2 and HDL3, and HDL with and without A-II)], d) susceptibility of LDL to oxidation, e) activities of lecithin cholesterol acyltransferase (LCAT) and cholesterol ester transfer protein, and f) rates of endogenous cholesterol synthesis.
The study was renewed in FY 2000 is to assess the impact of newer approaches to dietary modification with the intent of reducing the risk of developing cardiovascular disease. The specific aims of the study are as follow: 1) to assess the impact of substituting two classes of fats specifically formulated to substitute for hydrogenated fats (i.e., trans-free margarines and genetically modified/selectively bred oils) on serum lipid levels (total, VLDL, LDL, HDL, HDL2 and HDL3 cholesterol; triglyceride; apo A-l and B; Lp[a]), immune function, and prostaglandin levels, and 2) to address unresolved issues related to plant sterols, including the relative efficacy of currently available preparations, impact of the fat and cholesterol content of the diet, and effect of dosing frequency on serum lipids, endogenous cholesterol synthesis, cholesterol absorption, and fat soluble vitamin levels. Study subjects are older (50-75 y) hypercholesterolemic female and male subjects (LDL cholesterol 130-160 mg/dl). Each 5-week diet phase will be scheduled in randomized order; all food and drink will be provided. In Part 1, Study 1, subjects will consume each of 3 diets (30 percent fat [2/3 experimental fat], 80 mg cholesterol/1000 kcal) with the following experimental fats: conventional soft margarine; trans-free margarine (interesterified palm kernel + liquid oil); trans-free margarine (fully hydrogenated soybean oil + liquid oil). In Part 1, Study 2, subjects will consume each of 6 diets (as above) with the following experimental fats: hydrogenated soybean (shortening), high oleic sunflower, high oleic soybean, high oleic canola, low saturated soybean and low linolenic soybean oils. In Part 2, Study 1, subjects will consume each of 4 diets (38 percent fat [15 percent SFA, 14 percent MUFA, 6 percent PUFA], 200 mg cholesterol/1000 kcal), baseline and the following: sitostanol ester; sitostenol ester, and genetically modified high sterol oil. In Part 2, Study 2, subjects will consume each of 4 plant sterol enriched diets, high fat (as above) with high (200 mg) or low (80 mg) cholesterol/1000 kcal, and low fat (20 percent fat [5 percent SFA, 7.5 percent MUFA, 7.5 percent PUFA]) with high or low cholesterol. In Part 2, Study 3, the effect of dosing regime will be assessed using the most efficacious plant sterol as identified in Study 1 and diet as in Study 2 (single bolus or in 3 divided doses).
Study design
Who may qualify
- Ages
- Up to 100 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
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 8 Jan 2016.
- Background: PubMed 10704618Schwab US, Ausman LM, Vogel S, Li Z, Lammi-Keefe CJ, Goldin BR, Ordovas JM, Schaefer EJ, Lichtenstein AH. Dietary cholesterol increases the susceptibility of low density lipoprotein to oxidative modification. Atherosclerosis. 2000 Mar;149(1):83-90. doi: 10.1016/s0021-9150(99)00310-x.
- Background: PubMed 11026626Matthan NR, Raeini-Sarjaz M, Lichtenstein AH, Ausman LM, Jones PJ. Deuterium uptake and plasma cholesterol precursor levels correspond as methods for measurement of endogenous cholesterol synthesis in hypercholesterolemic women. Lipids. 2000 Sep;35(9):1037-44. doi: 10.1007/s11745-000-0616-9.
- Background: PubMed 11714853Matthan NR, Cianflone K, Lichtenstein AH, Ausman LM, Jauhiainen M, Jones PJ. Hydrogenated fat consumption affects acylation-stimulating protein levels and cholesterol esterification rates in moderately hypercholesterolemic women. J Lipid Res. 2001 Nov;42(11):1841-8.
- Background: PubMed 11290832Lichtenstein AH, Jauhiainen M, McGladdery S, Ausman LM, Jalbert SM, Vilella-Bach M, Ehnholm C, Frohlich J, Schaefer EJ. Impact of hydrogenated fat on high density lipoprotein subfractions and metabolism. J Lipid Res. 2001 Apr;42(4):597-604.
- Background: PubMed 10379016Lichtenstein AH, Ausman LM, Jalbert SM, Schaefer EJ. Effects of different forms of dietary hydrogenated fats on serum lipoprotein cholesterol levels. N Engl J Med. 1999 Jun 24;340(25):1933-40. doi: 10.1056/NEJM199906243402501.
- Background: PubMed 11893781Han SN, Leka LS, Lichtenstein AH, Ausman LM, Schaefer EJ, Meydani SN. Effect of hydrogenated and saturated, relative to polyunsaturated, fat on immune and inflammatory responses of adults with moderate hypercholesterolemia. J Lipid Res. 2002 Mar;43(3):445-52.
- Background: PubMed 11861668Lichtenstein AH, Ausman LM, Jalbert SM, Vilella-Bach M, Jauhiainen M, McGladdery S, Erkkila AT, Ehnholm C, Frohlich J, Schaefer EJ. Efficacy of a Therapeutic Lifestyle Change/Step 2 diet in moderately hypercholesterolemic middle-aged and elderly female and male subjects. J Lipid Res. 2002 Feb;43(2):264-73.
- Background: PubMed 14642411Lichtenstein AH, Erkkila AT, Lamarche B, Schwab US, Jalbert SM, Ausman LM. Influence of hydrogenated fat and butter on CVD risk factors: remnant-like particles, glucose and insulin, blood pressure and C-reactive protein. Atherosclerosis. 2003 Nov;171(1):97-107. doi: 10.1016/j.atherosclerosis.2003.07.005.
- Background: PubMed 12936917Mauger JF, Lichtenstein AH, Ausman LM, Jalbert SM, Jauhiainen M, Ehnholm C, Lamarche B. Effect of different forms of dietary hydrogenated fats on LDL particle size. Am J Clin Nutr. 2003 Sep;78(3):370-5. doi: 10.1093/ajcn/78.3.370.
- Background: PubMed 15087307Matthan NR, Welty FK, Barrett PH, Harausz C, Dolnikowski GG, Parks JS, Eckel RH, Schaefer EJ, Lichtenstein AH. Dietary hydrogenated fat increases high-density lipoprotein apoA-I catabolism and decreases low-density lipoprotein apoB-100 catabolism in hypercholesterolemic women. Arterioscler Thromb Vasc Biol. 2004 Jun;24(6):1092-7. doi: 10.1161/01.ATV.0000128410.23161.be. Epub 2004 Apr 15.
- Background: PubMed 15756215Gordon LB, Harten IA, Patti ME, Lichtenstein AH. Reduced adiponectin and HDL cholesterol without elevated C-reactive protein: clues to the biology of premature atherosclerosis in Hutchinson-Gilford Progeria Syndrome. J Pediatr. 2005 Mar;146(3):336-41. doi: 10.1016/j.jpeds.2004.10.064.
- Background: PubMed 15933247Matthan NR, Jalbert SM, Lamon-Fava S, Dolnikowski GG, Welty FK, Barrett HR, Schaefer EJ, Lichtenstein AH. TRL, IDL, and LDL apolipoprotein B-100 and HDL apolipoprotein A-I kinetics as a function of age and menopausal status. Arterioscler Thromb Vasc Biol. 2005 Aug;25(8):1691-6. doi: 10.1161/01.ATV.0000172629.12846.b8. Epub 2005 Jun 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.
Alice Lichtenstein
Tufts University
Questions about this trial
What is this clinical trial studying?
An observational study of Atherosclerosis and Cardiovascular Diseases, run by Tufts University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
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 8 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00005532, which also lists 12 linked publications.
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 8 Jan 2016.