Clinical trial NCT05295719: Combining HIIT and n-3 PUFA to Reduce Inflammation and Improve Metabolic Health
Official title: Combining Fish Oil and Exercise to Improve Obesity-associated Inflammation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Obesity
Inflammation
Human Microbiome
Insulin Resistance
Dyslipidemias
Lead sponsor: Texas Tech University
Sponsor class: OTHER
Collaborators: name: University of Houston
name: Texas Tech University Health Sciences Center
First posted: 2022-03-25
Enrollment: 120
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: The goal of this project is to understand the combined effects of fish oil and exercise in obesity-associated inflammation. The investigators hypothesize that fish oil will improve gut bacteria profiles, which will in turn potentiate the benefits of an exercise program and improve energy utilization and reduce inflammation and metabolic risk.

Detailed description: Incidence of obesity continues to increase in the United States and worldwide, making its prevention or reduction a public health priority. Nutrition research that can lead to effective prevention strategies is greatly needed. Inflammation is a major underlying cause for obesity, and it is imperative to understand how anti-inflammatory food sources, such as fish oil, could aid in reducing obesity. Moreover, exercise is effective at reducing systemic inflammation and improving insulin resistance. Both exercise and diet can influence health through changes in the gut microbiome; however, no studies have investigated how together these affect gut microbiome and overall metabolic health. The goal is to understand the combined effects of fish oil and exercise in obesity-associated inflammation. The investigators hypothesize that fish oil will improve gut bacteria profiles, which will in turn potentiate the benefits of an exercise program and improve energy utilization and reduce inflammation and metabolic risk. These studies will provide the foundation for development of novel strategies for obesity, inflammation, dyslipidemia and dysglycemia.

The first aim of this study will focus on determining the combined effects of n-3 PUFA and HIIT on improving metabolic risks such as obesity-related markers of inflammation, dyslipidemia, and insulin resistance.

The investigators will test the hypothesis that n-3 PUFA, in addition to HIIT, will have beneficial effects on energy utilization, as well as obesity-related markers of inflammation, dyslipidemia and insulin resistance.

Aim 2.1: Investigate the influence of n-3 PUFA and HIIT on body weight and composition Aim 2.2: Investigate the influence of n-3 PUFA and HIIT on serum markers associated with obesity Aim 2.3: Investigate influence of n-3 PUFA and HIIT on energy utilization/ markers of insulin resistance

The second aim is to determine the combined effects of n-3 polyunsaturated fatty acids (n-3 PUFA) and high-intensity interval training (HIIT) on improving gut dysbiosis.

The investigators will test the hypothesis that n-3 PUFA supplementation will improve gut microbiota composition and related metabolites, which will result in reduced inflammation and ameliorate the metabolic response to a HIIT exercise intervention in an overweight population.

Aim 1.1: Investigate the influence of n-3 PUFA and exercise on gut microbiota composition

Aim 1.2: Investigate the influence of n-3 PUFA and exercise on microbiota produced metabolites

Participants will be randomly allocated to 1 of 4 treatment groups (n = 120), each balanced for sex, BMI, lipid profile, and dietary intake. The goal is to conduct the study in smaller cohorts, such as 10-15 participants/group (n = 40-60).

Participants will first be allocated to two groups: One group will take 4 grams n-3 PUFA (AlaskOmega®) per day (3000 mg EPA and 1000 mg DHA) and one group will take placebo (safflower oil, AlaskOmega®, from Organic Technologies Inc.) for 8 weeks of initial supplementation.

Following this, one group from the treatment and one from the placebo group (creating 4 groups: (1) placebo + exercise control; (2) n-3 PUFA + exercise control; (3) placebo + HIIT; (4) n-3 PUFA + HIIT) will also participate in a home-based 4 x 4 HIIT exercise (4 intervals for 4 min at 85-95% HRmax with 3min active recovery at 50-70% HRmax) program 3 days/week conducted at a local gym under virtual investigator supervision and utilizing cycle ergometers.

If not asked to exercise, participants will be instructed to maintain their normal level of physical activity but will participate in a home-based, time-matched control consisting of flexibility training led virtually by investigators.

All participants will wear a heart rate monitor (Polar H10) provided by TTU throughout the training (HIIT and control) to monitor exertion level.

Capsules will be administered in a double-blind fashion and will be identical in appearance. Participants will visit the clinic to pick up capsules. To ensure compliance, subjects will be reminded via phone (text message or phone call based on participant preference) to take their capsules and counts will be conducted when they come in for study visits.

As with any acute metabolic or physiological improvements, beneficial effects of exercise on bacterial taxa and resultant metabolite production are quickly reversed with detraining. Thus, it is of interest to determine if fish consumption can ameliorate the negative metabolic and gut effects of detraining.

At the end of the 6-week intervention (week 14), participants in the respective groups will cease engaging in HIIT for a 2-week detraining period and those allocated to the fish oil group will receive recommendations for fish consumption according to guidelines (8 oz per week or consuming fish twice weekly, including one serving of oily fish). Dietary records for the last 2 weeks of the study will assess dietary fish intake compliance.

Eligibility criteria: Inclusion Criteria:

* 18-65 years old
* Overweight/ Obese (BMI ≥ 25 to ≤ 40 kg/m2)
* Elevated Triglycerides (\>150 mg/dL)
* Prediabetes (fasting blood glucose 100 to 125 mg/dl)

Exclusion Criteria:

* Diagnosed with Diabetes or liver disease.
* Taking BP or diabetes medications.
* Received antibiotics medications in the last 6 months.
* Pregnant/ lactating/ Irregular menstrual cycle/ menopausal.
* Currently following a formal/ structured weight loss program.
* Currently taking fish oil.
* Do not have access to smart phone/ computer with internet access.
* Exercise ≥ 1 time/week or a moderate-high score on the International Physical Activity Questionnaire.
* Feeling uncomfortable riding bike for 30 minutes.
* Claustrophobic or unable to stay under the hood for metabolic testing.

Primary outcomes:
measure: Mean Change from Baseline in Serum high-sensitivity C-reactive protein at 8 weeks
timeFrame: Post-Supplementation at week 8
measure: Mean Change from Baseline in Interleukin (IL)-6 at 8 weeks
timeFrame: Post-Supplementation at week 8
measure: Mean Change from Baseline in Interleukin (IL)-10 at 8 weeks
timeFrame: Post-Supplementation at week 8
measure: Mean Change from Baseline in Monocyte chemoattractant protein-1 at 8 weeks
timeFrame: Post-Supplementation at week 8
measure: Mean Change from Baseline in Tumor necrosis factor at 8 weeks
timeFrame: Post-Supplementation at week 8
measure: Mean Change from Baseline in Total Cholesterol at 8 weeks
timeFrame: Post-Supplementation at week 8
measure: Mean Change from Baseline in High-density lipoprotein (HDL)at 8 weeks
timeFrame: Post-Supplementation at week 8
measure: Mean Change from Baseline in Non-high-density lipoprotein (Non-HDL) at 8 weeks
timeFrame: Post-Supplementation at week 8
measure: Mean Change from Baseline in Low-density lipoprotein (LDL) at 8 weeks
timeFrame: Post-Supplementation at week 8
measure: Mean Change from Baseline in Very-low-density lipoprotein (VLDL) at 8 weeks
timeFrame: Post-Supplementation at week 8
measure: Mean Change from Baseline in Triglycerides at 8 weeks
timeFrame: Post-Supplementation at week 8
measure: Mean Change from Baseline in Total/HDL cholesterol at 8 weeks
timeFrame: Post-Supplementation at week 8
measure: Mean Change from Baseline in Fasting blood glucose at 8 weeks
timeFrame: Post-supplementation at week 8
measure: Mean Change from Baseline in Oral glucose tolerance test (OGTT) at 8 weeks
timeFrame: Post-supplementation at week 8
measure: Mean Change from Baseline in Insulin at 8 weeks
timeFrame: Post-supplementation at week 8
measure: Mean Change from Baseline in Total Body Fat Percentage at 8 weeks
timeFrame: Post-Supplementation at week 8
measure: Mean Change from Baseline in Body weigh at 8 weeks
timeFrame: Post-Supplementation at week 8
measure: Mean Change from Baseline in Skeletal Muscle Mass Percentage at 8 weeks
timeFrame: Post-Supplementation at week 8
measure: Mean Change from Baseline in Serum high-sensitivity C-reactive protein at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Baseline in Monocyte chemoattractant protein-1 at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Baseline in Interleukin (IL)-6 at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Baseline in Interleukin (IL)-10 at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Baseline in Tumor necrosis factor (TNF) at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Baseline in Total Cholesterol at 14 weeks
timeFrame: Post-intervention at week 14
measure: Mean Change from Baseline in High-density lipoprotein (HDL) at 14 weeks
timeFrame: Post-intervention at week 14
measure: Mean Change from Baseline in Non-high-density lipoprotein (Non-HDL) at 14 weeks
timeFrame: Post-intervention at week 14
measure: Mean Change from Baseline in Low-density lipoprotein (LDL) at 14 weeks
timeFrame: Post-intervention at week 14
measure: Mean Change from Baseline in Very-low-density lipoprotein (VLDL) at 14 weeks
timeFrame: Post-intervention at week 14
measure: Mean Change from Baseline in Triglycerides at 14 weeks
timeFrame: Post-intervention at week 14
measure: Mean Change from Baseline in total/HDL cholesterol at 14 weeks
timeFrame: Post-intervention at week 14
measure: Mean Change from Baseline in Fasting blood glucose at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Baseline in Oral glucose tolerance test (OGTT) at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Baseline in Insulin at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Baseline in Body weight at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Baseline in Total Body Fat Percentage at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Baseline in Skeletal Muscle Mass Percentage at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Baseline in Serum high-sensitivity C-reactive protein at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in Interleukin (IL)-6 at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in Interleukin (IL)-10 at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in Tumor necrosis factor (TNF) at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in Monocyte chemoattractant protein-1 at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in Total Cholesterol at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in High-density lipoprotein (HDL) at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in Non-high-density lipoprotein (Non-HDL) at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in Low-density lipoprotein (LDL) at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in Very-low-density lipoprotein (VLDL) at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in Total/HDL cholesterol at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in Triglycerides at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in Insulin at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in Fasting blood glucose at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in Oral glucose tolerance test (OGTT) at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in Skeletal Muscle Mass Percentage at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in Body weight at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in Total Body Fat Percentage at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Supplementation in Serum high-sensitivity C-reactive protein at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in Interleukin (IL)-6 at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in Interleukin (IL)-10 at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in Monocyte chemoattractant protein-1 at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in Tumor necrosis factor (TNF) at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in Total Cholesterol at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in Total/HDL cholesterol at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in High-density lipoprotein (HDL) at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in Non-high-density lipoprotein (Non-HDL) at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in Low-density lipoprotein (LDL) at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in Very-low-density lipoprotein (VLDL) at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in Triglycerides at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in Insulin at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in Oral glucose tolerance test (OGTT) at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in Fasting blood glucose at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in Body weight at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in Total Body Fat Percentage at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in Skeletal Muscle Mass Percentage at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Intervention in Serum high-sensitivity C-reactive protein at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in Tumor Necrosis Factor (TNF) at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in Interleukin (IL)-6 at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in Interleukin (IL)-10 at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in Monocyte Chemoattractant Protein-1 at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in Total Cholesterol at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in High-density lipoprotein (HDL) at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in Non-high-density lipoprotein (Non-HDL) at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in Low-density lipoprotein (LDL) at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in Very-low-density lipoprotein (VLDL) at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in Total/HDL cholesterol at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in Triglycerides at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in Insulin at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in Fasting blood glucose at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in Oral glucose tolerance test (OGTT) at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in Body weight at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in Total Body Fat Percentage at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in Skeletal Muscle Mass Percentage at 16 weeks
timeFrame: Post-Feeding at week 16
Secondary outcomes:
measure: Mean Change from Baseline in Bacterial Profile at 8 weeks
timeFrame: Post-Supplementation at week 8
measure: Mean Change from Baseline in Serum Acetate Profile at 8 weeks
timeFrame: Post-Supplementation at week 8
measure: Mean Change from Baseline in Fecal acetate Profile at 8 weeks
timeFrame: Post-Supplementation at week 8
measure: Mean Change from Baseline in Propionate Profile at 8 weeks
timeFrame: Post-Supplementation at week 8
measure: Mean Change from Baseline in Butyrate Profile at 8 weeks
timeFrame: Post-Supplementation at week 8
measure: Mean Change from Baseline in Markers of Serum lipopolysaccharides at 8 weeks
timeFrame: Post-Supplementation at week 8
measure: Mean Change from Baseline in Markers of Serum lipopolysaccharides-binding protein at 8 weeks
timeFrame: Post-Supplementation at week 8
measure: Mean Change from Baseline in Bacterial Profile at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Baseline in Serum Acetate Profile at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Baseline in Fecal acetate Profile at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Baseline in Propionate Profile at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Baseline in Butyrate Profile at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Baseline in Markers of Serum lipopolysaccharides at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Baseline in Markers of Serum lipopolysaccharides-binding protein at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Baseline in Serum Acetate Profile at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in Fecal acetate Profile at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in Bacterial Profile at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in Propionate Profile at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in Butyrate Profile at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in Markers of Serum lipopolysaccharides at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Baseline in Markers of Serum lipopolysaccharides-binding protein at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Supplementation in Bacterial Profile at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in Serum Acetate Profile at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in Fecal acetate Profile at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in Propionate Profile at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in Butyrate Profile at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in Markers of Serum lipopolysaccharides at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Supplementation in Markers of Serum lipopolysaccharides-binding protein at 14 weeks
timeFrame: Post-Intervention at week 14
measure: Mean Change from Post-Intervention in Bacterial Profile at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in Serum Acetate Profile at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in Fecal acetate Profile at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in Propionate Profile at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in Butyrate Profile at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in Markers of Serum lipopolysaccharides at 16 weeks
timeFrame: Post-Feeding at week 16
measure: Mean Change from Post-Intervention in Markers of Serum lipopolysaccharides-binding protein at 16 weeks
timeFrame: Post-Feeding at week 16
Other outcomes:
Locations:
Study officials:
affiliation: Texas Tech University
name: Kembra D Albracht-Schulte, Ph.D
role: PRINCIPAL_INVESTIGATOR
References: