Clinical trial NCT01636635: Effect of Age and Weight Loss on Inflammation and Iron Homeostasis
Official title: Effect of Age and Weight Loss on Obesity-related Inflammation and Iron Homeostasis in Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obesity
Aging
Lead sponsor: Tufts University
Sponsor class: OTHER
First posted: 2012-07-10
Enrollment: 44
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: The purpose of this study is to evaluate the effect of aging and weight loss on iron status and immune response in obese women. Iron deficiency and immune impairment are two of the numerous complications of obesity. The central hypothesis is that obesity-induced inflammation causes lower iron status through decreased iron absorption and availability in young and older obese women. Furthermore, the investigators hypothesize that this can be corrected with weight loss in both young and older obese women.

Detailed description: Obese individuals have chronic inflammation, higher risk of iron deficiency, and impaired immune response. These are conditions seen also with aging, but it is unknown to what extent they may be further impacted by obesity in the elderly. With this study the investigators aim to establish the mechanism by which weight loss may reduce inflammation and enhance iron status in young and older obese adults through the peptide hormone hepcidin, which regulates iron homeostasis. The investigators also aim to identify a possible link between iron homeostasis and immune response through hepcidin, which has been implicated in T cell mediated immunity. The investigators hypothesize that obesity-induced inflammation causes dysregulation of hepcidin expression leading to lower iron status through decreased iron absorption and availability in young and older adults. Furthermore, the investigators hypothesize that hepcidin dysregulation, and thus iron status can be mitigated with weight loss in both young and older obese adults. This hypothesis will be tested in obese young and older women undergoing weight loss through calorie restriction. Change in iron status, inflammation, and hepcidin will be determined before and after weight loss. Further, the impact of inflammatory environment of obesity on peripheral blood mononuclear cell hepcidin, ferroportin, intracellular iron, and T cell function in young and older adults will be determined. This study will address two important public health problems, i.e. obesity and iron deficiency and will be an important step toward the identification of strategies to enhance health of obese young and older adults.

Eligibility criteria: Inclusion Criteria:

* Enrolling patients in the Weight and Wellness Center (WWC) at Tufts Medical Center, part of their Tufts Employees, low calorie diet (LCD) or pre-surgical low calorie diet (PS-LCD) program, or enrolling at WWC as individual patients.
* BMI in the range of 30 to 55 kg/m2.
* Either ages 18-45 or \>60.

Exclusion Criteria:

* Pregnancy.
* Weight reduction greater than or equal to 3% in the past 3 months.
* Prior gastric restrictive surgery.
* Weight loss medications within the 4 weeks prior to screening.
* History of eating disorder.
* Renal disease (serum creatinine \>2mg/dl).
* Hepatic disease, except for nonalcoholic steatohepatitis (NASH).
* Celiac disease, or any kind of intestinal malabsorption disorders.
* Gastrointestinal cancer.
* Hereditary hemochromatosis, or any blood disorders.
* Chronic infectious or inflammatory disease.
* Use of immunosuppressants.
* Severe iron deficiency anemia (hemoglobin\<8 g/dl) or other conditions that would prevent them from discontinuing iron supplement use.
* Unwilling to discontinue iron supplement intake. The dietary plan recommended by the WWC will include daily intake of iron that meets the iron RDA for the subject's gender and age group, therefore discontinuing iron supplement will not be harmful for the participants. Intake of other supplements will not be an exclusion criteria, as long as it stays constant throughout the study period.

Primary outcomes:
measure: Change in serum hepcidin
timeFrame: Baseline and 12-16 weeks
measure: Change in inflammation (CRP, IL-6)
timeFrame: Baseline and 12-16 weeks
measure: Change in iron status
timeFrame: Baseline and 12-16 weeks
Secondary outcomes:
measure: Change in PBMC intracellular iron content
timeFrame: Baseline and 12-16 weeks
measure: Change in PBMC Hepcidin expression
timeFrame: Baseline and 12-16 weeks
measure: Change in PBMC ferroportin expression
timeFrame: Baseline and 12-16 weeks
measure: Change in PBMC subpopulations and proliferation
timeFrame: Baseline and 12-16 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: JM USDA Human Nutrition Research Center on Aging
state: Massachusetts
Study officials:
affiliation: Tufts University
name: Simin N Meydani, DVM, PhD
role: PRINCIPAL_INVESTIGATOR
References: