Genetic and Environmental Determinants of Triglycerides (GOLDN)

This study has been completed.
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
University of Alabama at Birmingham
ClinicalTrials.gov Identifier:
NCT00083369
First received: May 21, 2004
Last updated: November 16, 2013
Last verified: November 2013
  Purpose
To characterize the genetic basis of the variable response of triglycerides to two environmental contexts, one that raises triglycerides (dietary fat), and one that lowers triglycerides (fenofibrate treatment.)

Condition
Atherosclerosis
Cardiovascular Diseases
Heart Diseases

Study Type: Observational
Study Design: Time Perspective: Prospective

Further study details as provided by University of Alabama at Birmingham:

Primary Outcome Measures:
  • describe the association between blood lipids and gene variants [ Time Frame: 3 weeks after start of fenofibrate intervention // 3 weeks after start of fenofibrate intervention ] [ Designated as safety issue: No ]
    Blood lipids were measured by the following: triglyceride, high-density cholesterol, low-density cholesterol concentrations. We will describe the association between blood lipids and gene variants.


Enrollment: 1327
Study Start Date: September 2002
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Detailed Description:

BACKGROUND:

Hypertriglyceridemia is emerging as an important predictor of atherosclerosis, and recent evidence suggests related phenotypes of triglycerides (TGs), such as TG remnant particles and small lactate dehydrogenase (LDL) particles, are particularly atherogenic. There is considerable variation in the response of TGs and related phenotypes to the environment.

The study is in response to a Request for Applications (RFA) entitled " Interaction of Genes and Environment in Shaping Risk Factors for Heart, Lung, Blood, and Sleep Disorders". The RFA was released in October, 2001.

DESIGN NARRATIVE:

Measurements will be collected before and after a dietary fat challenge to assess postprandial TGs and related atherogenic phenotypes (VLDL TGs, chylomicron TGs, TG remnant particles, high-density lipoprotein(HDL) and low density lipids (LDL) particle sizes, total cholesterol, LDL-C, and HDL-C). In families with 2 or more members in a sibship with high TGs (>= 130 mg/dl), the authors will conduct a short-term, placebo-controlled, randomized trial of fenofibrate in all willing and eligible family members (anticipated sample size = 1,200). A two-period crossover design will be executed with a 2-week washout between two 3-week treatment periods (placebo or micronized fenofibrate, 160 mg). About 1,000 family members have a Marshfield genome marker set available as part of national Heart Lung and Blood (NHLBI) FHS; the remaining 1,400 will be typed using the same marker set. They will conduct genome-wide linkage analyses using state-of-the-art methods to localize novel genetic loci contributing to TG response in the context of fat loading and fenofibrate treatment. They will type 15 single nucleotide polymorphisms (SNPs) in ten candidate genes known to contribute to the response of TGs to dietary fat and fenofibrate, and create haplotypes for association studies. They will use combinatorial partitioning methods and neural networks to test association of the individual SNPs and haplotypes with response to the two environmental interventions. The identification of genetic loci that predict TG response in the presence of two disparate contexts, fat loading and fibrate therapy, may provide insights into genetic pathways (a) predisposing to hypertriglyceridemia, ultimately leading to avenues for primary prevention, and (b) predicting response to TG lowering, leading to new drug targets for hypertriglyceridemia.

  Eligibility

Ages Eligible for Study:   19 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Subjects meeting entry criteria
Criteria

Inclusion criteria:

  1. ≥18 years of age
  2. fasting TGs <1,500 mg/dl
  3. willingness to participate in the study and attend the scheduled clinic exams
  4. member of a family with at least two members in a sibship
  5. aspartate aminotransferase (AST) and alanine aminotransferase (ALT) results within normal range
  6. creatinine ≤2.0 mg/dl

Exclusion criteria:

  1. history of liver, kidney, pancreas, or gall bladder disease or malabsorption
  2. current pregnancy
  3. insulin use
  4. use of lipid-lowering drugs (including prescription, over the counter, and nutriceuticals; volunteers taking these agents were withdrawn from them at least 4 weeks prior to the study with physician's approval)
  5. use of warfarin
  6. women of childbearing potential not using an acceptable form of contraception
  7. known hyper-sensitivity to fenofibrate
  8. history of pancreatitis within 12 months prior to enrollment
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00083369

Sponsors and Collaborators
University of Alabama at Birmingham
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Donna Arnett University of Alabama at Birmingham
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Fretts AM, Follis JL, Nettleton JA, Lemaitre RN, Ngwa JS, Wojczynski MK, Kalafati IP, Varga TV, Frazier-Wood AC, Houston DK, Lahti J, Ericson U, van den Hooven EH, Mikkilä V, Kiefte-de Jong JC, Mozaffarian D, Rice K, Renström F, North KE, McKeown NM, Feitosa MF, Kanoni S, Smith CE, Garcia ME, Tiainen AM, Sonestedt E, Manichaikul A, van Rooij FJ, Dimitriou M, Raitakari O, Pankow JS, Djoussé L, Province MA, Hu FB, Lai CQ, Keller MF, Perälä MM, Rotter JI, Hofman A, Graff M, Kähönen M, Mukamal K, Johansson I, Ordovas JM, Liu Y, Männistö S, Uitterlinden AG, Deloukas P, Seppälä I, Psaty BM, Cupples LA, Borecki IB, Franks PW, Arnett DK, Nalls MA, Eriksson JG, Orho-Melander M, Franco OH, Lehtimäki T, Dedoussis GV, Meigs JB, Siscovick DS. Consumption of meat is associated with higher fasting glucose and insulin concentrations regardless of glucose and insulin genetic risk scores: a meta-analysis of 50,345 Caucasians. Am J Clin Nutr. 2015 Nov;102(5):1266-78. doi: 10.3945/ajcn.114.101238. Epub 2015 Sep 9.
Tanaka T, Ngwa JS, van Rooij FJ, Zillikens MC, Wojczynski MK, Frazier-Wood AC, Houston DK, Kanoni S, Lemaitre RN, Luan J, Mikkilä V, Renstrom F, Sonestedt E, Zhao JH, Chu AY, Qi L, Chasman DI, de Oliveira Otto MC, Dhurandhar EJ, Feitosa MF, Johansson I, Khaw KT, Lohman KK, Manichaikul A, McKeown NM, Mozaffarian D, Singleton A, Stirrups K, Viikari J, Ye Z, Bandinelli S, Barroso I, Deloukas P, Forouhi NG, Hofman A, Liu Y, Lyytikäinen LP, North KE, Dimitriou M, Hallmans G, Kähönen M, Langenberg C, Ordovas JM, Uitterlinden AG, Hu FB, Kalafati IP, Raitakari O, Franco OH, Johnson A, Emilsson V, Schrack JA, Semba RD, Siscovick DS, Arnett DK, Borecki IB, Franks PW, Kritchevsky SB, Lehtimäki T, Loos RJ, Orho-Melander M, Rotter JI, Wareham NJ, Witteman JC, Ferrucci L, Dedoussis G, Cupples LA, Nettleton JA. Genome-wide meta-analysis of observational studies shows common genetic variants associated with macronutrient intake. Am J Clin Nutr. 2013 Jun;97(6):1395-402. doi: 10.3945/ajcn.112.052183. Epub 2013 May 1.

Responsible Party: University of Alabama at Birmingham
ClinicalTrials.gov Identifier: NCT00083369     History of Changes
Other Study ID Numbers: 1250  U01HL072524-05 
Study First Received: May 21, 2004
Last Updated: November 16, 2013
Health Authority: United States: Federal Government

Additional relevant MeSH terms:
Cardiovascular Diseases
Heart Diseases
Atherosclerosis
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases

ClinicalTrials.gov processed this record on July 25, 2016