Clinical trial NCT04049162: Blueberry Enhances Activity and Cognition Through Increased Vascular Efficiency
Official title: Effects of Blueberry Consumption on Vascular Function, Physical Activity, and Cognition in Sedentary Older Adults
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sedentary Lifestyle
Blood Pressure
Arterial Stiffness
Overweight and Obesity
Keywords: Blueberries
Pulse Wave Velocity
Aging
Exercise
Cognition
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: U.S. Highbush Blueberry Council
First posted: 2019-08-08
Enrollment: 84
Sex: ALL
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Recent evidence suggests that increased berry intake results in a variety of health benefits, across multiple health domains. This 3-month randomized, double-blind, placebo-controlled trial assess the effects of combining daily blueberry intake with weekly exercise (BB-EX) on cardiovascular function, as well as physical activity and cognitive function, in sedentary older adults (\>60 years). We will compare these effects to the same outcomes with a control group consuming a blueberry placebo (P-EX) at 0, 4, 8 and 12 weeks.

Detailed description: A 12-week randomized, double-blind, placebo-controlled physical activity intervention will be administered in sedentary older (\>60 years) women and men randomized to either lyophilized blueberry powder, rehydrated and consumed as a beverage twice daily with meals (BB-EX; n = 25), or an indistinguishable placebo powder, taken in the same manner (placebo control; P-EX; n = 25).

Vascular function (primary outcome), 24-hr ambulatory blood pressure, cognitive performance, and related secondary measures will be assessed at 0 and 12 weeks; berry and nutrient intake and function are assessed every 4 weeks; and physical activity as step counts will be continuously monitored using a mobile device (Garmin). Blood, urine (24-hr), and stool samples will be collected at 0 and 12 weeks and archived for later analysis.

The 12-week study duration is based upon the timing of vascular responses seen in other trials, as well as the minimal time needed to expect a change in cognitive performance in an older adult population. The blueberry dose of 36 grams per day in a split dose consumed with meals is based on (1) a 33% increase in dose over that previously used in a longer (6-month) trial; (2) delivering the most effective dose of blueberry bioactives; and (3) reduced likelihood of any gastrointestinal symptoms.

Eligibility criteria: Inclusion Criteria:

* Age 60 and older
* Overweight (BMI ≥25 to 35 kg/m2)
* Well-controlled blood pressure (\< 150/90 mmHg)
* Able to speak and understand spoken and written English
* Cognitively normal (Mini-Cog score 3-5)
* Able to walk independently
* Social security number (required for compensation)
* Own a smartphone or other mobile device capable of downloading the Garmin Connect app

Exclusion Criteria:

* Exercise \> 150 minutes/week
* Unwillingness or inability to be randomized to any one of two intervention groups without knowing which (double-blind), submit to all study testing, or continuously participate in a randomly assigned diet and exercise intervention for six months.
* Unwilling to restrict consumption of anthocyanin-rich foods
* Unwillingness to abstain from mood altering drugs (including marijuana but excluding CBDs) for 7 days prior to baseline and endpoint testing.
* Self-reported vegetarian or vegan.
* Inability to complete written recording forms including journals of eating and exercise behaviors.
* Inability to complete written and computerized cognitive tasks (presented in English).
* Allergy or intolerance to blueberry or placebo powder ingredients Placebo ingredients include: maltodextrin, fructose, artificial blueberry flavor, natural blueberry flavor, artificial purple color (water, FD\&C Red #40, FD\&C Blue #1, malic acid, sodium benzoate) citric acid, and artificial red color (water, FD\&C Red #40, malic acid, sodium benzoate, silica dioxide).
* Gastrointestinal disorders that influence digestion and absorption of food, e.g., IBD
* History of frequent urinary tract or Clostridium difficile infections
* Presence of unstable, acutely symptomatic, or life-limiting illness.
* Regular use of medication that interferes with the measurement of study outcomes as determined by the study physician.
* Unstable use of medications, other than statins, for conditions associated with metabolic syndrome (hypertension, diabetes, dyslipidemia) during the prior 6 months or during the study.
* Antibiotic use in the last 3 months.
* Cigarette smoking, chewing, or use of nicotine replacement products in the past 3 months or during the course of the study.
* Colonoscopy in last 2 months.
* History of stomach or bowel resection (other than appendectomy), gastric bypass or other bariatric weight loss procedure effecting absorption.
* History of significant weight instability (defined as \> 10 pounds weight gain or loss over one month prior to study participation).
* History of cancer treatment (other than melanoma skin cancer) and not "cancer-free" for at least 1 year.
* History of anti-hormonal therapy (eg., for breast or prostate cancer) within the last 6 months.

Primary outcomes:
measure: Change from baseline in pulse wave velocity at 12 weeks
timeFrame: 0 to 12 weeks
Secondary outcomes:
measure: Change from baseline in cognitive flexibility at 12 weeks
timeFrame: 0 to 12 weeks
measure: Change from baseline in physical activity at 12 weeks
timeFrame: 0 to 12 weeks
measure: Change from baseline in ambulatory blood Pressure at 12 weeks
timeFrame: 0 to 12 weeks
measure: Change from baseline in total calories at 4, 8 and 12 weeks
timeFrame: 0 to 12 weeks (0, 4, 8 and 12 weeks)
measure: Change from baseline in macronutrient intake at 4, 8 and 12 weeks
timeFrame: 0 to 12 weeks (0, 4, 8 and 12 weeks)
measure: Change from baseline in micronutrient intake at 4, 8 and 12 weeks
timeFrame: 0 to 12 weeks (0, 4, 8 and 12 weeks)
measure: Change from baseline aerobic endurance at 4, 8, and 12 weeks
timeFrame: 0 to 12 weeks (0, 4, 8 and 12 weeks)
measure: Change from baseline hand grip strength at 4, 8 and 12 weeks
timeFrame: 0 to 12 weeks (0, 4, 8 and 12 weeks)
Other outcomes:
measure: Change from baseline in central arterial pressure at 12 weeks
timeFrame: 0 to 12 weeks
measure: Baseline dietary intake (Total calories)
timeFrame: 0 weeks
measure: Baseline dietary intake (macronutrient intake)
timeFrame: 0 weeks
measure: Baseline dietary intake (micronutrient intake)
timeFrame: 0 weeks
measure: Change from baseline in body weight
timeFrame: 0 to 12 weeks
measure: Height at baseline
timeFrame: 0 weeks
measure: Seated blood pressure at baseline
timeFrame: 0 weeks
measure: Change from baseline verbal memory at 12 weeks
timeFrame: 0 to 12 weeks
measure: Change from baseline Executive Function at 12 weeks
timeFrame: 0 to 12 weeks
measure: Change from baseline processing speed at 12 weeks
timeFrame: 0 to 12 weeks
measure: Change from baseline reaction time at 12 weeks
timeFrame: 0 to 12 weeks
measure: Change from baseline paired associates learning at 12 weeks
timeFrame: 0 to 12 weeks
measure: Change from baseline spatial working memory at 12 weeks
timeFrame: 0 to 12 weeks
measure: Change from baseline pattern recognition memory at 12 weeks
timeFrame: 0 to 12 weeks
measure: Change from baseline delayed matching to sample at 12 weeks
timeFrame: 0 to 12 weeks
measure: Change from baseline rapid visual information processing at 12 weeks
timeFrame: 0 to 12 weeks
measure: Adherence to diet supplementation by weekly package return count
timeFrame: 0 to 12 weeks
Locations:
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
Study officials:
affiliation: Duke University
name: William Kraus, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Miller MG, Hamilton DA, Joseph JA, Shukitt-Hale B. Dietary blueberry improves cognition among older adults in a randomized, double-blind, placebo-controlled trial. Eur J Nutr. 2018 Apr;57(3):1169-1180. doi: 10.1007/s00394-017-1400-8. Epub 2017 Mar 10.
citation: Michalska A, Lysiak G. Bioactive Compounds of Blueberries: Post-Harvest Factors Influencing the Nutritional Value of Products. Int J Mol Sci. 2015 Aug 10;16(8):18642-63. doi: 10.3390/ijms160818642.
citation: Whyte AR, Cheng N, Fromentin E, Williams CM. A Randomized, Double-Blinded, Placebo-Controlled Study to Compare the Safety and Efficacy of Low Dose Enhanced Wild Blueberry Powder and Wild Blueberry Extract (ThinkBlue) in Maintenance of Episodic and Working Memory in Older Adults. Nutrients. 2018 May 23;10(6):660. doi: 10.3390/nu10060660.
citation: Johnson SA, Figueroa A, Navaei N, Wong A, Kalfon R, Ormsbee LT, Feresin RG, Elam ML, Hooshmand S, Payton ME, Arjmandi BH. Daily blueberry consumption improves blood pressure and arterial stiffness in postmenopausal women with pre- and stage 1-hypertension: a randomized, double-blind, placebo-controlled clinical trial. J Acad Nutr Diet. 2015 Mar;115(3):369-377. doi: 10.1016/j.jand.2014.11.001. Epub 2015 Jan 8.
citation: Reis JF, Monteiro VV, de Souza Gomes R, do Carmo MM, da Costa GV, Ribera PC, Monteiro MC. Action mechanism and cardiovascular effect of anthocyanins: a systematic review of animal and human studies. J Transl Med. 2016 Nov 15;14(1):315. doi: 10.1186/s12967-016-1076-5.