Clinical trial NCT03228550: Omega-3 Fatty Acids and Exercise on Mobility and Cognition in Older Women
Official title: Investigating the Effects of Omega-3 Fatty Acid Multinutrient Supplement and Exercise on Mobility and Cognition in Older Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Aging
Cognitive Decline
Keywords: omega-3 fatty acid
B vitamins
vitamin E
Phosphatidylserine
Gingko biloba
Gait
Aerobic Exercise
Memory
Cognitive function
Lead sponsor: Bournemouth University
Sponsor class: OTHER
Collaborators: name: Efamol Ltd
name: Sylvia Waddilove Foundation
First posted: 2017-07-25
Enrollment: 60
Sex: FEMALE
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: There are two interventions, a multi-nutrient dietary supplement and exercise. The study will have four groups; 1. multi-nutrient supplement and exercise, 2. multi-nutrient non-exercise, 3. placebo supplement and exercise and 4. placebo supplement non-exercise.
Primary purpose: PREVENTION

Brief summary: The study will provide insight into how lifestyle-related interventions, specifically nutrition and exercise can impact the health of older women. The study uses a unique combination of interventions and encapsulates overall health outcomes by measuring both mobility and cognitive function.

The study examines the effects of a combined omega-3 polyunsaturated fatty acid (PUFA) and multi-nutrient supplement on measures of mobility and cognition in women aged 60 years and above. Volunteers for the study will be randomly assigned to one of four groups which are as follows:

* Omega-3 PUFA multi-nutrient supplement and aerobic exercise
* Omega-3 PUFA multi-nutrient supplement and no exercise
* Placebo supplement and aerobic exercise
* Placebo supplement and no exercise

Volunteers undertake the dietary supplementation for a period of 24 weeks. The active dietary supplement contains a daily dosage of 1 g docosahexaenoic acid, 160 mg eicosapentaenoic acid, 240 mg Ginkgo biloba, 60 mg phosphatidylserine, 20 mg d-α tocopherol, 1 mg folic acid, and 20 µg vitamin B12. The placebo supplement contains an iso-calorific oil blend that is typical of the current UK diet. The aerobic exercise consists of two classes per week the final 12 weeks of the study on stationary spinning exercise bikes.

Volunteers attend testing at the beginning and after 24 weeks. Verbal memory, spatial working memory, executive function and processing speed are assessed via a battery of cognitive tests. Mobility testing comprises three walking tests, some under single and dual task paradigms, as well as the five times sit to stand test, a measure of dynamic balance and functional mobility. Volunteers also provide two blood samples, one for fatty acids analysis and the other serum homocysteine levels. Participants also complete health-related quality of life questionnaire, the short form 36 (SF36) questionnaire, food diary and food frequency questionnaire.

Detailed description: Design and Setting:

The study is a randomized semi-blinded, placebo-controlled trial in females aged 60 years and over. The study examines the effects of a high docosahexaenoic acid omega-3 PUFA multi-nutrient dietary supplement and aerobic exercise, both on their own and in combination, on outcomes related to mobility and cognition. All measurements and data collection, as well as the aerobic exercise, take place at the same study site (Bournemouth University, United Kingdom), with participants instructed to consume the dietary supplement at home.

Blinding Randomization and Allocation:

The dietary supplements are packed in identical containers and coded by the Principal Investigator, who has no involvement in the data collection. Omega-3 PUFA capsules have a distinct odor, therefore a small amount of fish oil is added to the placebo capsules to help maintain blinding. A stratified block randomization design is followed with stratification based on frailty classification of non-frail or pre-frail, followed by permuted block randomization. Randomization is achieved by creating a computer-generated list of numbers consisting of four blocks for each stratum referred to without specification of the intervention group (e.g., A, B, C, and D). The list is generated and stored by the Principal Investigator. Due to the nature of the exercise intervention participants are only be blinded to the dietary intervention; however, the experimenters are blinded to the exercise group allocations.

Participants:

Participants are recruited through local newspaper advertisements and public engagements in Bournemouth, U.K. The public advertisements include a brief study description as well as the contact details for the research team. Those who are interested receive a participant information document including the design, procedure, benefits, and risks of the study. Before any data is collected, all participants provide signed written informed consent forms.

All participants are screened to assess frailty status, according to the Fried et al. (2001) criteria. The criteria include low muscle strength, self-reported exhaustion, slowed gait speed, low levels of physical activity, and unintentional weight loss. A score of zero out of the five indicates non-frail, one or two pre-frail, and three or above frail.

The Mini Mental State Examination (MMSE) is performed to exclude participants with cognitive impairment, as this has the potential to go undiagnosed. The test is performed according to British Psychology Society guidelines, and is not used for diagnostic purposes and individual results are not be disclosed to any participant. Participants who score ≤24 are excluded from the study.

Demographic Information:

Information on the age, height, weight, verbal intelligence and medication use is collected from each participant. Information on medications is self-reported, with both type and number of medications recorded. The national adult reading test (NART) is used to assess verbal intelligence. The test requires participants to read aloud 50 pre-prepared words, with scores being calculated based on the number of correct pronunciations. Minor variations from the pronunciations are not penalized as the aim of the test is to assess familiarity with the words rather than exact pronunciation.

Sample Size:

Sample size was determined based on the primary outcome of habitual gait speed. The sample size calculation was based on a difference of 0.08 m/sec with a power of 0.8 and α of 0.05 (two-tailed), based on previous research (Strike et al. 2016). A minimum sample size of 25 participants per group is required to detect an effect size d of 0.8 between experimental groups and the control. An overall recruitment target of 120 participants, 30 per group has been set to allow for drop-outs.

Analysis will be carried out on the basis of groups as randomly assigned. This intention-to-treat analysis will include participants who decide to discontinue treatment, but take part in assessment at 24 weeks. Data analysis will be performed at the conclusion of the intervention and include data collected at baseline and 24 weeks. Data will be tested for normal distribution using Shapiro-Wilk test and Q-Q-plots. Associations between baseline levels of serum homocysteine, whole-blood DHA levels and cognitive and mobility outcomes will be made, as well as changes in DHA and measures of mobility and cognition at the end of the intervention. The treatment effects of the two interventions over time (from pre- and post-measurements) will be analyzed by 2 X 2 ANOVA, with demographic and health information, such as age and NART score, and changes in serum homocysteine and changes in blood fatty acids examined as covariates. This analysis will be performed on all primary and secondary outcomes. Effect size will also be calculated. In all analyses P\<0.05 will be considered significant.

Eligibility criteria: Inclusion Criteria:

* Able to walk 50 meters unassisted
* Non-frail or pre-frail according to Fried frailty phenotype

Exclusion Criteria:

* Vestibular impairments
* Diagnosed neurological disorder
* Mini mental state examination score of ≤24
* History of lower limb surgery
* Seafood allergy
* Regular consumption of multivitamin/fish oil supplements within six months prior to baseline measurements
* Previously received advice from a health care professional to not take part in strenuous exercise.

Primary outcomes:
measure: Change in habitual gait speed
timeFrame: Baseline and 24 weeks post intervention
Secondary outcomes:
measure: Change in executive function
timeFrame: Baseline and 24 weeks post intervention
measure: Change in verbal memory
timeFrame: Baseline and 24 weeks post intervention
measure: Change in processing speed
timeFrame: Baseline and 24 weeks post intervention
measure: Change in spatial working memory
timeFrame: Baseline and 24 weeks post intervention
measure: Change in fast walking speed
timeFrame: Baseline and 24 weeks post intervention
measure: Change in dual task walking speed
timeFrame: Baseline and 24 weeks post intervention
measure: Change in dual Task Cost
timeFrame: Baseline and 24 weeks post intervention
measure: Change in five times sit to stand
timeFrame: Baseline and 24 weeks post intervention
measure: Change in physical functioning from short form 36 questionnaire
timeFrame: Baseline and 24 weeks post intervention
measure: Change in bodily pain from short form 36 questionnaire
timeFrame: Baseline and 24 weeks post intervention
measure: Change in role limitations due to physical health problems from short form 36 questionnaire
timeFrame: Baseline and 24 weeks post intervention
measure: Change in role limitations due to personal or emotional problems from short form 36 questionnaire
timeFrame: Baseline and 24 weeks post intervention
measure: Change in emotional well-being from short form 36 questionnaire
timeFrame: Baseline and 24 weeks post intervention
measure: Change in social functioning from short form 36 questionnaire
timeFrame: Baseline and 24 weeks post intervention
measure: Change in energy/fatigue from short form 36 questionnaire
timeFrame: Baseline and 24 weeks post intervention
measure: Change in general health perceptions from short form 36 questionnaire
timeFrame: Baseline and 24 weeks post intervention
Other outcomes:
measure: Change in whole-blood fatty acid content
timeFrame: Baseline and 24 weeks post intervention
measure: Change in serum homocysteine
timeFrame: Baseline and 24 weeks post intervention
measure: Change in stride length
timeFrame: Baseline and 24 weeks post intervention
measure: Change in cadence
timeFrame: Baseline and 24 weeks post intervention
measure: Change in double support phase percentage
timeFrame: Baseline and 24 weeks post intervention
measure: Change in stride length variability
timeFrame: Baseline and 24 weeks post intervention
measure: Physical activity levels
timeFrame: Baseline and 24 weeks post intervention
measure: Dietary energy intake
timeFrame: Baseline and 24 weeks post intervention
measure: Carbohydrate intake from diet
timeFrame: Baseline and 24 weeks post intervention
measure: Protein intake from diet
timeFrame: Baseline and 24 weeks post intervention
measure: Fat intake from diet
timeFrame: Baseline and 24 weeks post intervention
measure: Omega-3 polyunsaturated fatty acid intake from diet
timeFrame: Baseline and 24 weeks post intervention
Locations:
city: Bournemouth
country: United Kingdom
facility: Bournemouth University
state: Dorset
Study officials:
affiliation: Bournemouth University
name: Simon C Dyall, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Bournemouth University
name: Fotini Tsofliou, PhD
role: STUDY_DIRECTOR
References:
citation: Fried LP, Tangen CM, Walston J, Newman AB, Hirsch C, Gottdiener J, Seeman T, Tracy R, Kop WJ, Burke G, McBurnie MA; Cardiovascular Health Study Collaborative Research Group. Frailty in older adults: evidence for a phenotype. J Gerontol A Biol Sci Med Sci. 2001 Mar;56(3):M146-56. doi: 10.1093/gerona/56.3.m146.
citation: Strike SC, Carlisle A, Gibson EL, Dyall SC. A High Omega-3 Fatty Acid Multinutrient Supplement Benefits Cognition and Mobility in Older Women: A Randomized, Double-blind, Placebo-controlled Pilot Study. J Gerontol A Biol Sci Med Sci. 2016 Feb;71(2):236-42. doi: 10.1093/gerona/glv109. Epub 2015 Aug 11.
citation: Dyall SC. Long-chain omega-3 fatty acids and the brain: a review of the independent and shared effects of EPA, DPA and DHA. Front Aging Neurosci. 2015 Apr 21;7:52. doi: 10.3389/fnagi.2015.00052. eCollection 2015.
citation: Dyall SC. Methodological issues and inconsistencies in the field of omega-3 fatty acids research. Prostaglandins Leukot Essent Fatty Acids. 2011 Nov;85(5):281-5. doi: 10.1016/j.plefa.2011.04.009. Epub 2011 Sep 16.
citation: Fairbairn P, Tsofliou F, Johnson A, Dyall SC. Combining a high DHA multi-nutrient supplement with aerobic exercise: Protocol for a randomised controlled study assessing mobility and cognitive function in older women. Prostaglandins Leukot Essent Fatty Acids. 2019 Apr;143:21-30. doi: 10.1016/j.plefa.2019.04.001. Epub 2019 Apr 1.