Fat Gain and Cardiovascular Disease Mechanisms
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|ClinicalTrials.gov Identifier: NCT00589498|
Recruitment Status : Completed
First Posted : January 9, 2008
Last Update Posted : November 4, 2013
Understanding the mechanisms of obesity-induced hypertension is important both for prevention and therapy. Studies of patients with established obesity have provided valuable information on pathophysiologic links between obesity and both blood pressure and cardiovascular risk. However, these studies are necessarily limited by the heterogeneity of obesity-associated disease so that the relative contribution of obesity or hypertension or other co-existing diseases to specific regulatory abnormalities is often not clear. Clarification of whether any abnormalities associated with increased cardiovascular risk were present before or after the development of obesity has also been problematic.
We therefore propose a series of novel studies directed at establishing the effects of increased body fat in otherwise healthy individuals. We will determine the distribution patterns of increased body fat and how both increased body fat and fat distribution relate to changes in blood pressure, and in neural, endothelial and inflammatory mechanisms which have been implicated in the development and progression of cardiac and vascular disease.
We will study non-obese subjects with and without a family history of hypertension. These subjects will undergo an eight-week program of overfeeding with the objective of inducing a 4 kg fat gain. We will determine the nature of fat distribution in these individuals after the fat gain program and subsequently after an eight-week period of weight loss and restoration of normal body weight. Measurements will be compared to those obtained in a matched control group with and without a family history of hypertension, who will continue their normal diets. We will test the following hypotheses:
- Individuals with a family history of hypertension will gain more visceral fat and upper body subcutaneous fat and will have greater blood pressure increases with overfeeding- compared with those without such a family history.
- For all overfed subjects, increases in blood pressure and insulin resistance with fat gain will be most marked in those individuals with a predominantly upper body and visceral fat accumulation.
- Upper body and visceral fat gain will also be associated with greater impairment in cardiovascular function, higher nocturnal blood pressures and an increased likelihood of sleep disordered breathing.
|Condition or disease||Intervention/treatment||Phase|
|Hypertension Sleep Apnea Syndromes Obesity||Dietary Supplement: 1000 extra calories||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||69 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|Official Title:||Fat Gain and Cardiovascular Disease Mechanisms|
|Study Start Date :||December 2005|
|Actual Primary Completion Date :||December 2012|
|Actual Study Completion Date :||December 2012|
Subjects who are randomized to overfeed will visit with the General Clinical Research Center dieticians as often as necessary to gain 2 kg of fat (about 4 kg overall) over a period of 8 weeks.
Dietary Supplement: 1000 extra calories
Each subject received 1000 kcal/d in addition to weight maintenance requirements. The diet composition throughout the study was 40% carbohydrate, 40% fat, and 20% protein.
No Intervention: 2
Subjects who are randomized to non-overfeeding will continue with their normal diet and activity levels for a period of 8 weeks.
- Individuals with a family history of hypertension will gain more visceral fat and upper body subcutaneous fat and will have greater blood pressure increases with overfeeding- compared with those without such a family history. [ Time Frame: conclude the 180 patients recruited ]
- * For all overfed subjects, increases in blood pressure and insulin resistance with fat gain will be most marked in those individuals with a predominantly upper body and visceral fat accumulation. [ Time Frame: after recruiting at least 70 patients ]
- Upper body and visceral fat gain will also be associated with greater impairment in cardiovascular function, higher nocturnal blood pressures and an increased likelihood of sleep disordered breathing [ Time Frame: Recruit at least 70 subjects ]
- Increased weight gain, particularly in the upper body and visceral regions, will be accompanied by enhanced production of inflammatory mediators linked to cardiovascular risk, including adhesion molecules and C-reactive protein. [ Time Frame: Recruit at least 70 patients ]
- These changes will resolve with subsequent loss of weight at the end of the overfeeding program and restoration of normal body fat and fat distribution. [ Time Frame: Recruit at least 70 patients ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00589498
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Virend K Somers, MD, PhD||Mayo Clinic|