Enhancing Adaptations to Exercise

Researchers are trying to understand how chronic inflammation affects muscle function and responses to exercise.They are also trying to determine if suppressing chronic inflammation using omega-3 fatty acids (n3-PUFA) restores skeletal muscle function and exercise responsiveness in older adults.

Study Overview

• Status: Completed
• Conditions: Inflammation
• Intervention / Treatment: Diagnostic test: Body Composition Scan; Drug: n3-PUFA; Procedure: Biopsy; Drug: Placebo

Detailed Description

Participants will be divided into two groups. Men and women between the ages of 20-35 years and 65-85 years. Participants in the older age group will be randomly assigned to receive groups (n3-PUFA or placebo (soybean oil)) in a double-blind manner. Before and after the intervention, all participants will complete an outpatient study day (body composition, blood draw, treadmill test, strength test) and an inpatient study day (muscle biopsies, fat biopsies, indirect calorimetry, exercise test, mixed meal test). During the intervention phase of the study, participants will be instructed to swallow 2 softgels twice per day with meals (morning and evening) for a total of 4 softgels per day. Every 4 weeks, participants will report to the Clinical Research and Trials Unit (CRTU) to pick up a new prescription and return any remaining capsules from the previous prescription. On the day they pick up prescription refills, participants will report to the CRTU for a fasting blood sample. The duration of the intervention will be 6 months.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic in Rochester

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion criteria:

• Men and women between the ages of 20-35 years
• Men and women between the ages of 65-85 years

Exclusion criteria:

• Regular use of omega-3 nutritional supplements
• Diabetes or fasting plasma glucose > or equal to 126 mg/dL
• Anemia (female subjects hemoglobin of <11 g/dl and male subjects hemoglobin <12 g/dl)
• Active coronary artery disease or history of unstable macrovascular disease (unstable angina, myocardial infarction, stroke, and revascularization of coronary, peripheral or carotid artery within 3 months of recruitment)
• Renal failure (serum creatinine > 1.5mg/dl)
• Chronic active liver disease (AST>144 IU/L or ALT>165 IU/L)
• Oral warfarin group medications or history of blood clotting disorders.
• international normalized ratio (INR) >2.01.5
• Smoking
• Pregnancy or breastfeeding
• Alcohol consumption greater than 2 glasses/day or other substance abuse
• Untreated or uncontrolled hypothyroidism
• Debilitating chronic disease (at the discretion of the investigators)
• Fish or shellfish allergy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: n3-PUFA; Participants will be instructed to swallow 2 Docosahexaenoic acid (DHA)/EPA soft gels twice per day with meals (morning and evening) for a total of 4 soft gels per day.	Diagnostic test: Body Composition Scan; Measure of body fat percentage, skeletal muscle mass, body water, and visceral fat.; Other Names: DEXA (dual-energy X-ray absorptiometry) scan.; Drug: n3-PUFA; The DHA/EPA softgels will each contain ~465mg of EPA and ~375mg of DHA for a total daily dosage of 3.4g/day. Additionally, each capsule will contain SCI's proprietary Advance Lipid TechnologiesTM (ALTTM) containing the surfactants polysorbate 80, NF (~381 mg) and poloxamer 237, NF (~8.8 mg).; Procedure: Biopsy; Two muscle biopsies from the upper part of one leg. A small (~1cm) incision will be made through the skin, and a needle will then be used to remove the muscle.
Placebo Comparator: Placebo; Participants will be instructed to swallow 2 placebo soft gels twice per day with meals (morning and evening) for a total of 4 soft gels per day.	Diagnostic test: Body Composition Scan; Measure of body fat percentage, skeletal muscle mass, body water, and visceral fat.; Other Names: DEXA (dual-energy X-ray absorptiometry) scan.; Procedure: Biopsy; Two muscle biopsies from the upper part of one leg. A small (~1cm) incision will be made through the skin, and a needle will then be used to remove the muscle.; Drug: Placebo; Looks exactly like the study drug but contains soybean oil with no active ingredient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Maximum Workload Muscle Strength	Single-leg knee extensor strength was measured on a pneumatic resistance leg extension machine (Keiser Air300, Keiser Corporation, Fresno, CA, USA) and defined as the unilateral 1-repetition maximum (1-RM). Subjects performed a unilateral knee extension warm-up consisting of 10 repetitions at minimal resistance and 3 sets of 5-10 repetitions at increasing workloads. Subjects then performed a series of single repetition attempts at increasing workloads, each separated by 3 min of rest, until the maximum load that could be moved through the entire range of motion was reached. This maximum workload was defined as the individual 1-RM.	baseline, 6 months
Body Mass Index (BMI)	Subject's BMI calculated as weight in kilograms divided by height in meters squared. Uses measurements of height and weight obtained during study (with appropriate metric conversions). Measured as kg/m^2	baseline, 6 months
Body Fat	Dexa Scan based body fat, measured as a percentage of body weight	baseline, 6 months
Lean Body Mass	Lean body mass as measured by a DEXA scan is the amount of soft tissue that is not fat or bone. Measured in kilograms.	baseline, 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
C-Reactive Protein (CRP)	C-reactive protein is a substance produced by the liver in response to inflammation. Normal CRP levels are below 3.0 mg/L.Units: mg/L	baseline, 6 months
Erythrocyte Sedimentation Rate (ESR)	ESR is a blood test that can reveal inflammatory activity in the body. It measures the distance red blood cells fall in a test tube in one hour. The farther the red blood cells have descended, the greater the inflammatory response of the immune system. Normal results: < 16 years: < 10 mm/hr;Male < 50 years: < 15 mm/hr;Male > 50 years: < 20 mm/hr;Female < 50 years: < 20 mm/hr;Female > 50 years: < 30 mm/hr	baseline, 6 months
Weight	Subjects calculated weight in kilograms	baseline, 6 months

Collaborators and Investigators

• Sponsor: Mayo Clinic
• Collaborators: National Institute on Aging (NIA); National Center for Research Resources (NCRR)
• Investigators: Principal Investigator: Ian R Lanza, PhD, Mayo Clinic

Publications and helpful links

General Publications

• Moosavi D, Vuckovic I, Kunz HE, Lanza IR. A Randomized Trial of omega-3 Fatty Acid Supplementation and Circulating Lipoprotein Subclasses in Healthy Older Adults. J Nutr. 2022 Jul 6;152(7):1675-1689. doi: 10.1093/jn/nxac084.

Helpful Links

• Mayo Clinic Clinical Trials

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2018
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: November 13, 2017
• First Submitted That Met QC Criteria: November 17, 2017
• First Posted (Actual): November 22, 2017

Study Record Updates

• Last Update Posted (Estimated): November 14, 2023
• Last Update Submitted That Met QC Criteria: October 23, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Exercise; muscle function
• Additional Relevant MeSH Terms: Pathologic Processes; Inflammation
• Other Study ID Numbers: 17-004403; UL1RR024150 (U.S. NIH Grant/Contract); R01AG054454 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No