STRB: A Study of Strawberries and Disease Risk

• Sponsor: Clinical Nutrition Research Center, Illinois Institute of Technology (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01199848
• Collaborator: California Strawberry Commission (Other)
• Enrollment: 29
• Location: 1
• Arms: 5
• Actual Duration (Months): 61
• Patients Per Site Per Month: 0.5

Study Details

Study Description

Brief Summary

The purpose of this study is to test whether compounds found in strawberries (polyphenolics which are typically found in berry products, tea, coffee, red wine, and chocolate) will help reduce insulin resistance and inflammation, known factors in your blood associated with disease risk, when eaten with a standard high fat/carbohydrate meal.

Condition or Disease	Intervention/Treatment	Phase
Nutritional and Metabolic Diseases; Inflammation; Physiological Responses	Dietary Supplement: Placebo; Dietary Supplement: 10G; Dietary Supplement: 20G; Dietary Supplement: 40G; Dietary Supplement: Placebonofiber	N/A

Detailed Description

The main study is a single-center, randomized, cross-over, 4-arm, dose-response, single- blinded, 6-hour postprandial study to evaluate the ability of strawberry powder to block meal-induced oxidative stress and inflammation and concomitantly improve postprandial insulin sensitivity and glucose handling.

A planned sample size of 45 will be recruited into the study. Thirty subjects for the main study and 15 subjects for the complement study. Subjects can participate in both studies and if subjects participate in both studies, there will be a time gap between the main study and the complement study due to the volume of blood permitted to collect within 56 days.

The complement study will be a 2-arm placebo controlled study following the exact same protocol as the main study, but using only one strawberry dose (Dose 3 as in the main study) and comparing the effects relative to a placebo that does not control for fiber.

The main study will take 5- 6 weeks per subject to complete and the complement study will take 1-2 weeks per subject to complete, depending on subject's schedule.

The procedures conducted at the screening visit include blood sampling by finger prick for a fasting blood sugar test and anthropometric measurements (height, weight, and waist circumference), vital sign measurements (blood pressure and heart rate) and completion of a series of questionnaires relating to volunteers' general health and eating habits. Volunteers may be asked to complete an oral glucose/sugar tolerance test (OGTT) at screening. Volunteers will be exempt from the OGTT procedure if other qualifying conditions are present. Briefly, subjects undergoing OGTT will be asked to drink a glucose drink (similar in taste to kool-aid) in the morning after a 10 hour fast. Blood glucose finger pricks will then be done at 1 hour and 2 hours for determination of glucose tolerance. If the OGTT is necessary, additional compensation will be provided.

If qualified, subjects will undergo a 7-day pre-study period during which they will be asked to record their usual diet intake for 3 days, including 2 weekdays and 1 weekend day, EITHER followed by randomization into 1 of 4 treatment beverage sequences for the main study: Placebo (Pbo), Strawberry Dose 1, Strawberry Dose 2 and Strawberry Dose 3, OR followed by randomization into 1 of 2 treatment (Placebo without fiber and Strawberry Dose 3) beverage sequences for the complement study.

We expect it to be very difficult to eliminate or severely restrict polyphenolic diet during the entire study period, therefore subjects will be asked to limit only berry product intake during the study period. However, subjects will be asked to limit all polyphenolic foods in their diet for 3 days prior to each study visit.

All subjects will consume the standard high fat/ carbohydrate meal (known to induce oxidative- and inflammatory- stress) accompanied by 1 of 4 test beverages (whole milk shake with or without strawberry powder) on four separate occasions for the main study OR 1 of 2 test beverages on two separate occasions for the complement study, so that each subject will serve as their own control.

Subjects will arrive at the study visits fasted for at least 10 hours, well hydrated and rested. Each study visit will require blood draws throughout the visit. After pre-study procedures (height, weight, waist circumference, blood pressure, blood glucose finger prick) and while fasting, a registered nurse (RN) will place a catheter (flexible tubing) in subjects' arm for the purpose of drawing blood. This catheter will remain only throughout the study day. Approximately 1 tablespoon of blood will be taken at this time. The test meal and strawberry shake will be served and thereafter subjects will have blood draws (1 T each time) at designated time points for the next 6 hours. Each visit will last approximately 7 hours and subjects will be required to remain at the Clinical Nutrition Research Center on the IIT Campus for the duration of the visit. Blood samples will be collected at designated time points during the postprandial period for analysis of metabolic (insulin and glucose homeostasis), oxidative and inflammatory endpoint markers.

Study Design

• Study Type: Interventional
• Actual Enrollment: 29 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Single (Participant)
• Primary Purpose: Basic Science
• Official Title: Effect of Strawberry on Oxidative Stress- and Inflammatory-mediated Insulin Resistance (IR) in Humans: Combating a Major Risk Factor for Diabetes and Cardiovascular Disease Through Diet
• Actual Study Start Date: Sep 15, 2010
• Actual Primary Completion Date: Oct 15, 2015
• Actual Study Completion Date: Oct 15, 2015

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Pbo	Dietary Supplement: Placebo; whole milk shake without strawberry powder served with the high fat/carbohydrate test meal; Other Names: Pbo
Experimental: 10G STRB powder Dose 1	Dietary Supplement: 10G; whole milk shake with 10g strawberry powder served with the high fat/carbohydrate test meal; Other Names: Dose 1
Experimental: 20G STRB powder Dose 2	Dietary Supplement: 20G; whole milk shake with 20 strawberry powder served with the high fat/carbohydrate test meal; Other Names: Dose 2
Experimental: 40G STRB powder Dose 3	Dietary Supplement: 40G; whole milk shake with 40g strawberry powder served with the high fat/carbohydrate test meal; Other Names: Dose 3
Placebo Comparator: PlacebonoFiber Placebo without fiber	Dietary Supplement: Placebonofiber; Placebo without Fiber

Outcome Measures

Primary Outcome Measures

1. Postprandial Insulin Levels for 6 Hours [6 hour postprandial study over 4 periods]

   Strawberry dose-response effect on Postprandial glycemic control in insulin resistant individuals.plasma insulin concentration is measured over 6 hours by Randox clinical analyzer, analyzed with SAS mixed model.

Secondary Outcome Measures

1. Strawberry Dose-response Effect on Postprandial Oxidative Stress (Ox-LDL) in Insulin-resistant Men and Women in an Acute Postprandial Paradigm [6 hours postprandial study over 4 periods(treatments)]

   Postprandial plasma Ox-LDL concentration was measured by ELISA method. Normalizing responses to subjects own baseline (Time 0) was analyzed by SAS mixed model.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

Eligible volunteers must meet ONE or MORE of the criteria (numbers 1-4) associated with insulin resistance along with all of the other criteria listed (numbers 5-9):

1. Blood glucose concentration between140-199 mg/dL at 2hr from OGTT.

2. Elevated fasting glucose (≥110 mg/dL and <126 mg/dL)

3. Elevated fasting insulin (>75th percentile cutoff of 13.13 μU/mL)

4. Insulin resistance defined by the homeostasis model assessment method of insulin resistance (HOMA-IR) (glucose [in millimoles per liter] × insulin [in microunits per milliliter]/22.5) values of at least 2.5.

5. Waist circumference >102 cm (men) and > 88 cm (women) for screening visit invitation because many epidemiology studies have been shown that waist circumferences may be related to insulin resistance.

6. Nonsmokers

7. Not taking any medications that would interfere with outcomes of the study, i.e. lipid lowering medications, anti-inflammatory drugs, or dietary supplements

8. 18 years of age and older

9. No clinical evidence of cardiovascular, metabolic, respiratory, renal, gastrointestinal or hepatic disease

Exclusion Criteria:

• Pregnant and/or lactating

• Allergy or intolerance to strawberries and dairy products.

• Current regular consumption of strawberries is > 2 servings per day.

• Fasting blood glucose ≥ 126 mg/dL. Subjects identified with elevated fasting blood glucose levels will be advised to contact their primary care physician for appropriate follow-up care.

• Taking over the counter antioxidant supplements or other supplements that may interfere with the study procedures or endpoints.

• Subjects with unusual dietary habits (e.g. pica).

• Actively losing weight or trying to lose weight (unstable body weight fluctuations of

5 kg in a 60 day period).

• Excessive exercisers or trained athletes.

• Subjects with documented atherosclerotic disease, inflammatory disease, diabetes mellitus, or other systemic diseases.

• Addicted to drugs and/or alcohol.

• Medically documented psychiatric or neurological disturbances.

• Smoker (past smoker may be allowed if cessation is > 2 years)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Clinical Nutrition Research Center	Chicago	Illinois	United States	60616

Sponsors and Collaborators

• Clinical Nutrition Research Center, Illinois Institute of Technology
• California Strawberry Commission

Investigators

• Principal Investigator: Indika Edirisinghe, PhD, Institute for Food Safety and Health
• Principal Investigator: Britt Burton-Freeman, PhD, MS, Institute for Food Safety and Health

Study Documents (Full-Text)

None provided.

More Information

Publications

• Burton-Freeman B, Linares A, Hyson D, Kappagoda T. Strawberry modulates LDL oxidation and postprandial lipemia in response to high-fat meal in overweight hyperlipidemic men and women. J Am Coll Nutr. 2010 Feb;29(1):46-54.

• Responsible Party: Clinical Nutrition Research Center, Illinois Institute of Technology
• ClinicalTrials.gov Identifier: NCT01199848
• Other Study ID Numbers: STRB 2010-033
• First Posted: Sep 13, 2010
• Last Update Posted: Feb 12, 2021
• Last Verified: Jan 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Clinical Nutrition Research Center, Illinois Institute of Technology: nutrition; polyphenolic; strawberry; insulin resistance; metabolic syndrome
• Additional relevant MeSH terms: Metabolic Diseases; Inflammation

Study Results

Participant Flow

Recruitment Details	The study was conducted in Chicago, IL, USA from September 2010 to January 2013.
Pre-assignment Detail	7-day pre-study period: Following the screening visit, qualified subjects were asked to record their usual diet intake for 3 days, including 2 weekdays and 1 weekend day in order to know their usual intake and to coach them on what foods in their diet are rich in polyphenolics, especially 3 days prior to their each study visit.

Arm/Group Title	All Study Participants
Arm/Group Description	All participants received all 4 interventions (Placebo, STRB 10g, STRB 20g, and STRB 40g) in a randomized sequence Placebo: whole milk shake without strawberry powder served with the high fat/carbohydrate test meal Dose 1-10G: whole milk shake with 10g strawberry powder served with the high fat/carbohydrate test meal Dose 2- 20G: whole milk shake with 20 strawberry powder served with the high fat/carbohydrate test meal Dose 3-40G: whole milk shake with 40g strawberry powder served with the high fat/carbohydrate test meal
Period Title: Placebo Arm
STARTED	29
COMPLETED	21
NOT COMPLETED	8
Period Title: Placebo Arm
STARTED	21
COMPLETED	21
NOT COMPLETED	0
Period Title: Placebo Arm
STARTED	21
COMPLETED	21
NOT COMPLETED	0
Period Title: Placebo Arm
STARTED	21
COMPLETED	21
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Participants
Arm/Group Description	All participants received all 4 interventions (Placebo, STRB 10g, STRB 20g, and STRB 40g) in a randomized sequence Placebo: whole milk shake without strawberry powder served with the high fat/carbohydrate test meal Dose 1-10G: whole milk shake with 10g strawberry powder served with the high fat/carbohydrate test meal Dose 2- 20G: whole milk shake with 20 strawberry powder served with the high fat/carbohydrate test meal Dose 3-40G: whole milk shake with 40g strawberry powder served with the high fat/carbohydrate test meal
Overall Participants	21
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	39.8 (13.8)
Sex: Female, Male (Count of Participants)
Female	16 76.2%
Male	5 23.8%
Region of Enrollment (Count of Participants)
United States	21 100%

Outcome Measures

1. Primary Outcome

Title	Postprandial Insulin Levels for 6 Hours
Description	Strawberry dose-response effect on Postprandial glycemic control in insulin resistant individuals.plasma insulin concentration is measured over 6 hours by Randox clinical analyzer, analyzed with SAS mixed model.
Time Frame	6 hour postprandial study over 4 periods

Outcome Measure Data

Analysis Population Description

study completer who finished all 4 treatments.

Arm/Group Title	Placebo	10G STRB Powder	20G STRB Powder	40G STRB Powder
Arm/Group Description	Pbo Placebo: whole milk shake without strawberry powder served with the high fat/carbohydrate test meal	Dose 1 10G: whole milk shake with 10g strawberry powder served with the high fat/carbohydrate test meal	Dose 2 20G: whole milk shake with 20 strawberry powder served with the high fat/carbohydrate test meal	Dose 3 40G: whole milk shake with 40g strawberry powder served with the high fat/carbohydrate test meal
Measure Participants	21	21	21	21
Mean (Standard Error) [microIU/mL]	63.9 (5.6)	64.3 (5.6)	60.2 (5.6)	56.3 (5.6)

2. Secondary Outcome

Title	Strawberry Dose-response Effect on Postprandial Oxidative Stress (Ox-LDL) in Insulin-resistant Men and Women in an Acute Postprandial Paradigm
Description	Postprandial plasma Ox-LDL concentration was measured by ELISA method. Normalizing responses to subjects own baseline (Time 0) was analyzed by SAS mixed model.
Time Frame	6 hours postprandial study over 4 periods(treatments)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	10G STRB Powder	20G STRB Powder	40G STRB Powder
Arm/Group Description	Pbo Placebo: whole milk shake without strawberry powder served with the high fat/carbohydrate test meal	Dose 1 10G: whole milk shake with 10g strawberry powder served with the high fat/carbohydrate test meal	Dose 2 20G: whole milk shake with 20 strawberry powder served with the high fat/carbohydrate test meal	Dose 3 40G: whole milk shake with 40g strawberry powder served with the high fat/carbohydrate test meal
Measure Participants	21	21	21	21
Mean (Standard Error) [U/L]	-0.1 (0.8)	-0.3 (0.8)	-3 (0.8)	-0.17 (0.8)

Adverse Events

Time Frame	3 years
Arm/Group Title	Placebo		10G STRB Powder		20G STRB Powder		40G STRB Powder
Arm/Group Description	Pbo Placebo: whole milk shake without strawberry powder served with the high fat/carbohydrate test meal		Dose 1 10G: whole milk shake with 10g strawberry powder served with the high fat/carbohydrate test meal		Dose 2 20G: whole milk shake with 20 strawberry powder served with the high fat/carbohydrate test meal		Dose 3 40G: whole milk shake with 40g strawberry powder served with the high fat/carbohydrate test meal
All Cause Mortality
	Placebo		10G STRB Powder		20G STRB Powder		40G STRB Powder
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/21 (0%)		0/21 (0%)		0/21 (0%)
Serious Adverse Events
	Placebo		10G STRB Powder		20G STRB Powder		40G STRB Powder
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/21 (0%)		0/21 (0%)		0/21 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		10G STRB Powder		20G STRB Powder		40G STRB Powder
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		0/21 (0%)		0/21 (0%)		0/21 (0%)

Limitations/Caveats

The study had the following limitations: the study was single blinded and lack of data on other non-anthocyanin strawberry polyphenols and their metabolites may yield additional insight on the relationship between strawberry polyphenols & bioactivity

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.