Diet and Metabolic Inflammation

Obesity Clinical Trial

Official title:

Diet and Metabolic Inflammation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02539355
• Other study ID #: NCI2P30CA015704
• Secondary ID: CCSG Y39 Pilot:
• Status: Completed
• Phase: N/A
• First received: August 27, 2015
• Last updated: October 20, 2016
• Start date: August 2015
• Est. completion date: September 2016

Study information

• Verified date: October 2016
• Source: Fred Hutchinson Cancer Research Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Obesity is a risk factor for several common cancers, including those of the breast, colon, liver, and pancreas. Proposed molecular links between obesity and these types of cancer include systemic inflammation, hyperinsulinemia, and changes in the serum concentrations of sex steroid hormones and adipokines. All of these are strongly linked to low-grade chronic inflammatory processes in expanded adipose tissue. The objective of this proposal is to test the hypothesis that adipose tissue inflammation can be reduced by the foods we eat.

Description:

Overweight or obese individuals with evidence of insulin resistance will be enrolled, until 16 have completed all study procedures. Enrolled subjects will be randomized to follow one of two healthy diets for 12 weeks to determine how each diet affects inflammation in the body and sugar and insulin levels in the blood.

We will address the following specific aims:

Primary specific aim: To investigate whether the consumption of either diet reduces the metabolic activation of adipose tissue macrophages (ATM) as assessed by quantifying the ATM cell surface expression (relative mean fluorescence intensity, rMFI) of the metabolic activation markers, CD36 and ABCA1.

Secondary specific aim 1: To compare how each of the study diets affects endpoints downstream of metabolic activation of ATM, specifically (a) adipose tissue expression of the key pro-inflammatory cytokines tumor necrosis factor α (TNFα) and interleukins (IL)-1 beta and 6; (b) adipose tissue expression of the key anti-inflammatory adipokine, adiponectin; (c) systemic insulin sensitivity, as assessed by the Matsuda-DeFronzo Insulin Sensitivity Index (ISI), based on a 3-hour frequently sampled oral glucose tolerance test (FS-OGTT); and oral glucose tolerance, as assessed by measuring the total area-under-the-curve glucose in the FS-OGTT.

Secondary specific aim 2: To compare the impact of each of the study diets on low-grade chronic systemic inflammation, as assessed by measuring the concentrations of high sensitivity C-reactive protein (hsCRP), IL-6, and total adiponectin in fasting plasma.

Secondary specific aim 3: To assess dietary adherence in the two dietary intervention groups. Dietary adherence will be measured by a dietary adherence score (separately for each diet), based on repeated 4-day diet records completed by all participants in the study.

Because all of our study endpoints are thought to be linked to the gut microbiota, and because the effects of diet may be mediated through changes in the gut microbiota, we will also collect stool samples from all participants before and after completing the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: September 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Body Mass Index (BMI) = 28 kg/m2

• Homeostasis model assessment insulin resistance (HOMA-IR) index > 2.0

• Body weight within 10% of weight 3 months before starting the study

• Able to come to the FHCRC Prevention Center for one 1-hour pre-study visit and two clinic visits of ~4.5 hours duration each

• Able and willing to attend bi-weekly dietary group counseling sessions at FHCRC during the 12-week intervention period

• Willingness and ability to follow the dietary regimen

• Able to complete repeated 3-day food records before and during the dietary intervention.

• Willingness to maintain usual lifestyle habits (other than diet) throughout the study (e.g., physical activity habits)

• Ability to understand, speak, and write in English

• Ability to provide informed written consent

Exclusion Criteria:

• Any previous or current use of antidiabetic medications or insulin

• Presence or history of major chronic inflammatory or autoimmune disease (e.g., lupus, rheumatoid arthritis, Hashimoto's thyroiditis, inflammatory bowel disease, celiac disease, multiple sclerosis), malabsorption syndromes, or diseases of the liver, thyroid, or kidneys (stage IV or later chronic kidney disease)

• Food allergies or intolerances against major study foods

• Intake of drugs likely to interfere with study endpoints, including corticosteroids and anabolic steroids, hormone replacement therapy, NSAIDS (more than 3 times per week and/ or more than 600 mg per day), warfarin (within 3 months of starting the study), antibiotics or probiotics (within 2 weeks of starting the study)

• Presence or recent history of anemia (within 3 months of starting the study)

• Participation in another study that includes an intervention of any kind or a blood draw >300 mL over 3 months

• Alcohol intake > 2 drinks per day

• Use of tobacco products, eCigarettes, or recreational drugs on more than 2 days per month

• Current or recent (within 12 months of starting the study) pregnancy or breastfeeding

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Cancer
• Diabetes
• Inflammation
• Insulin Resistance
• Obesity

Intervention

Other:
• Diet A
12-week diet
• Diet B
12-week Diet

Locations

Country	Name	City	State
United States	Fred Hutchinson Cancer Research Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Fred Hutchinson Cancer Research Center

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Dietary adherence to prescribed 12-week diet assessed by dietary compliance score	Assessed by dietary compliance score, based on data from repeated 4-day dietary records	Assessed at the end of the study (week 12).	No
Other	Changes in gut microbiota assessed by stool sample analysis	Assessed by stool sample analysis	Change between beginning (day 1) and end (week 12) of the study diet period.	No
Primary	Change in adipose tissue macrophage cell surface expression of metabolic activation marker CD36 as measured by relative mean fluorescence intensity	As measured by relative mean fluorescence intensity (rMFI) on abdominal subcutaneous adipose tissue macrophages	Change between beginning (day 1) and end (week 12) of the study diet period.	No
Primary	Change in adipose tissue macrophage cell surface expression of metabolic activation marker ABCA1 as measured by relative mean fluorescence intensity (rMFI)	As measured by relative mean fluorescence intensity (rMFI) on abdominal subcutaneous adipose tissue macrophages	Change between beginning (day 1) and end (week 12) of the study diet period.	No
Secondary	Change in adipose tissue expression of the key pro-inflammatory cytokine, tumor necrosis factor a (TNFa) assessed by qPCR	Assessed by qPCR on whole abdominal subcutaneous adipose tissue	Change between beginning (day 1) and end (week 12) of the study diet period.	No
Secondary	Change in adipose tissue expression of the key pro-inflammatory cytokine, interleukin-6 (IL-6) assessed by qPCR	Assessed by qPCR on whole abdominal subcutaneous adipose tissue	Change between beginning (day 1) and end (week 12) of the study diet period.	No
Secondary	Change in adipose tissue expression of the key pro-inflammatory cytokine, interleukin-1 beta (IL-1beta) assessed by qPCR	Assessed by qPCR on whole abdominal subcutaneous adipose tissue	Change between beginning (day 1) and end (week 12) of the study diet period.	No
Secondary	Change in adipose tissue expression of the key anti-inflammatory adipokine, adiponectin assessed by qPCR	Assessed by qPCR on whole abdominal subcutaneous adipose tissue	Change between beginning (day 1) and end (week 12) of the study diet period.	No
Secondary	Change in systemic insulin sensitivity assessed by the Matsuda-DeFronzo Insulin Sensitivity Index	Assessed by the Matsuda-DeFronzo Insulin Sensitivity Index (ISI) based on a 3-hour frequently sampled oral glucose tolerance test (FS-OGTT)	Change between beginning (day 1) and end (week 12) of the study diet period.	No
Secondary	Change in oral glucose tolerance assessed by measuring total area under the curve glucose in the FS-OGTT	Assessed by measuring total area under the curve glucose in the FS-OGTT	Change between beginning (day 1) and end (week 12) of the study diet period.	No
Secondary	Change in fasting plasma C-reactive protein assessed by immunonephelometry	Assessed by immunonephelometry	Change between beginning (day 1) and end (week 12) of the study diet period.	No
Secondary	Change in fasting plasma IL-6 assessed by high-sensitivity ELISA	Assessed by high-sensitivity ELISA	Change between beginning (day 1) and end (week 12) of the study diet period.	No
Secondary	Change in fasting plasma total adiponectin assessed by ELISA	Assessed by ELISA	Change between beginning (day 1) and end (week 12) of the study diet period.	No