The Effects of Fish Oil Supplements During Supervised Exercise Therapy in Patients With Intermittent Claudication (FISHTIC)

Intermittent claudication (IC) is caused by peripheral arterial disease and has a high morbidity and mortality. Etiologic factors are similar to those of cardiovascular disease. Primary treatment consists of cardiovascular risk management and improvement of functional capacity with supervised exercise therapy (SET). A potential additional therapy is the administration of fish oil supplements containing high amounts of omega-3 Poly Unsaturated Fatty Acids (PUFAs). In earlier clinical and experimental trials omega-3 PUFA's improved hemorheological parameters such as erythrocyte deformability and aggregation, and a number of cardiovascular risk factors. Hemorheological parameters determine the blood flow in the microcirculation, which is of main importance in patients with IC since the macrocirculation is compromised. Inflammation is considered an important etiologic factor in the pathogenesis of atherosclerosis and contributes to peripheral arterial disease Since omega-3 PUFAs also have a strong anti-inflammatory effect, they might be effective in patients with IC by lowering the inflammatory response. In addition, visceral fat rather than obesity in general has been recognised as an etiologic and prognostic factor in atherosclerosis.

We hypothesise that the administration of omega-3 PUFA's in patients with IC has a synergistic effect with SET and improves walking distance after SET, by improving hemorheological parameters resulting in a better microcirculation. Second, we hypothesise that omega-3 PUFA's result in a less proinflammatory of whole blood in response to ex vivo stimulation with endotoxin. Third, we hypothesise that omega-3 PUFA's and SET result in a decrease in visceral fat mass.

Study Overview

• Status: Terminated
• Conditions: Intermittent Claudication
• Intervention / Treatment: Drug: Omega-3 fatty acids

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Noord Holland
    • Alkmaar, Noord Holland, Netherlands, 1800AM
      • Medical Center Alkmaar

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥ 18
• Newly diagnosed intermittent claudication
• Ankle Brachial Index < 0.8 at rest or > 0.15 decrease after exercise
• Able to perform standardised treadmill walking test for 2 min
• Written informed consent

Exclusion Criteria:

• Unable to fill out a questionnaire (cognitive impairment or insufficient knowledge of the Dutch language)
• Heart failure or unstable cardiac status (angina pectoris class III or IV or recent myocardial infarction < 3 months)
• Any illness with rapid evolution or a life expectancy < 3 months
• Recent cerebrovascular accident (< 3 months)
• Current use of fish oil supplements or > 2 times a week dietary fish
• Pregnancy
• Fish, soybean or peanut allergy
• Contra indications for the use of omega-3 fatty acids
• Use of oral anticoagulants (coumarin derivatives)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Supervised Exercise Therapy; Standard treatment: Supervised Exercise Therapy during 12 weeks	Drug: Omega-3 fatty acids; 1000 mg of omega-3 fatty acid ethylesters, 2 times daily, for 4 weeks, followed by 12 weeks of supervised exercise therapy in combination with 2 times daily omega-3 fatty acid supplementation.; Other Names: Fish oil supplements
NO_INTERVENTION: Controlled group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximal walking distance with standardised treadmill test	After 12 weeks of supervised exercise therapy

Secondary Outcome Measures

Outcome Measure	Time Frame
Hemorheological parameters	After 12 weeks of supervised exercise therapy
Visceral fat mass	After 12 weeks of supervised exercise therapy
Ex vivo cytokine production after stimulation with lipopolysaccharide	After 12 weeks of supervised exercise therapy
Assessment of the microcirculation with side stream dark field technology	After 12 weeks of supervised exercise therapy

Other Outcome Measures

Outcome Measure	Time Frame
Bloodpressure, heart rate, cholesterol, triglycerides, hemoglobin, leucocytes, C-reactive protein, ankle brachial index,	After 12 weeks of supervised exercise therapy

Collaborators and Investigators

• Sponsor: Medical Center Alkmaar
• Investigators: Principal Investigator: Alexander P.J. Houdijk, Dr., Medical Center Alkmaar

Study record dates

Study Major Dates

• Study Start (ACTUAL): December 1, 2014
• Primary Completion (ACTUAL): February 1, 2016
• Study Completion (ACTUAL): February 1, 2016

Study Registration Dates

• First Submitted: May 28, 2014
• First Submitted That Met QC Criteria: May 28, 2014
• First Posted (ESTIMATE): June 2, 2014

Study Record Updates

• Last Update Posted (ACTUAL): July 31, 2018
• Last Update Submitted That Met QC Criteria: July 28, 2018
• Last Verified: July 1, 2018

More Information

Terms related to this study

• Keywords: Cardiovascular risk; Fish oil supplements; Walking distance; Supervised Exercise Training; Hemorheological factors
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Intermittent Claudication
• Other Study ID Numbers: NL46719.029.13