Insulin ResistanceCIRCLESNCT02035592
The Health Effects of Blueberry Anthocyanins in Metabolic Syndrome (the CIRCLES-study)
A study testing Full dose blueberry and Half dose blueberry in people with Insulin Resistance and Metabolic Syndrome X, run by University of East Anglia at 4 sites in 2 countries.
Trial summary
The purpose of this study is to determine the dose-dependent impact of 6 month freeze-dried blueberry powder intake on insulin sensitivity and resistance, cardiovascular disease risk factors, and lung and cognitive function in overweight and obese participants with metabolic syndrome. Read more about this study
- Who is it for?
- Ages 50 to 74 years
- Conditions the study is for
- Insulin Resistance, Metabolic Syndrome X
- What is being tested?
- Full dose blueberry and Half dose blueberry
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 144 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Jan 2014to 7 Nov 2016
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and postmenopausal women (≥ 1 year since last menstruation)
- 50 to 75 years old
- BMI of ≥ 25 kg/m2
- 3 characteristics of metabolic syndrome i.e: Waist circumference ≥ 102 cm for men, ≥ 88 cm for women; Triglycerides ≥ 1.7 mmol/L (or drug treatment for elevated triglycerides); HDL-cholesterol < 1.0 mmol/L for men, < 1.3 mmol/L for women (or drug treatment for low HDL-cholesterol); Blood pressure ≥ 130 mm Hg systolic and/or ≥ 85 mm Hg diastolic blood pressure; Fasting blood glucose ≥ 5.56 mmol/L
- Successful biochemical, haematological and urinalysis assessment at screening
Who cannot join
- Current smokers, or ex-smokers ceasing < 6 months ago
- Existing or significant past medical history of vascular disease or medical conditions likely to affect the study measures
- Fructose intolerance or known allergies to the intervention treatments
- On therapeutic diets or having experienced substantial weight loss within 3 months of screening
- Taking flavonoid containing supplements (and unwilling to cease intake during, and 1 month preceding the trial)
- Planning on altering consumption of vitamin supplements / fish oil capsules during the course of the study.
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- Prescribed hypoglycaemic, vasodilators or HRT medication.
- Unsatisfactory biochemical, haematological or urinary assessment at screening, or measures considered to be counter indicative for the study
- < 3 characteristics of the metabolic syndrome.
- NB: REC approved NoSA granted to include those on anti-hypertensives (29JUL2014)
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
United Kingdom3 sites
Addenbrooke's hospital
Cambridge, Cambridgeshire, CB2 0QQ
Norwich Medical School University of East Anglia
Norwich, Norfolk, NR4 7TJ
Norfolk and Norwich University Hospital
Norwich, Norfolk, NR4 7UY
United States1 site
Harvard School of Public Health
Boston, Massachusetts, 02115
About this study
Official title: The Effects of Blueberry Anthocyanins on Insulin Resistance and Vascular, Lung and Cognitive Function in a Population With Metabolic Syndrome.
The purpose of this study is to determine the dose-dependent impact of 6 month freeze-dried blueberry powder intake on insulin sensitivity and resistance, cardiovascular disease risk factors, and lung and cognitive function in overweight and obese participants with metabolic syndrome. We will also examine acute post-prandial effects of blueberry intake (at baseline and at 6-months).
- Conditions
- Insulin Resistance, Metabolic Syndrome X
- Being tested
- Full dose blueberry, Half dose blueberry, Control
- Medical subject headings
- Insulin Resistance, Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Full dose blueberryOther
Full dose: 26g of freeze dried blueberry powder to be incorporated into the habitual diet.
Dietary restrictions will be observed (i.e. avoidance of blueberry, and restricted intake of anthocyanin rich foods) for 21 days prior to the first assessment visit and throughout the study.
Half dose blueberryOther
Half dose: 26g of freeze dried powder (containing 13g of freeze dried blueberry powder and 13g of placebo comparator material) to be incorporated into the habitual diet.
Dietary restrictions will be observed (i.e. avoidance of blueberry, and restricted intake of anthocyanin rich foods) for 21 days prior to the first assessment visit and throughout the study.
ControlOther
Control: 26g of placebo comparator material to be incorporated into the habitual diet.
Dietary restrictions will be observed (i.e. avoidance of blueberry, and restricted intake of anthocyanin rich foods) for 21 days prior to the first assessment visit and throughout the study.
| Study group | Role | What they receive |
|---|---|---|
| Full dose blueberry | Active comparator | 26g of freeze dried blueberry powder; equivalent to 2 portions of fresh blueberries per day.
Frequency: 26g per day.
Total duration: 6-month. Receives: Other: Full dose blueberry |
| Half dose blueberry | Active comparator | 26g of freeze dried powder; containing 13g of freeze dried blueberry powder and 13g of placebo comparator material; equivalent to 1 portion of fresh blueberries per day.
Frequency: 26g per day.
Total duration: 6-month. Receives: Other: Half dose blueberry |
| Control | Placebo comparator | Matched control powder; matched for appearance, taste and sugar content.
Frequency: 26g per day.
Total duration: 6-month. Receives: Other: Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin resistance
Assessed, in the fasted state, via HOMA-IR calculation in all participants; indirect assessment.
Measured: Chronic (0 to 6 month)
Secondary outcomes (8)
Insulin resistance
Assessed in a sub-group via hyperinsulinemic euglycaemic clamp.
Measured: Chronic (0 to 6 month)
Blood pressure and blood vessel regulation
Measurements taken of arterial stiffness, endothelial function and blood pressure.
Measured: Chronic (0 to 6 month)
Lung function
Assessed via standard spirometry techniques and biological assessment of exhaled samples.
Measured: Chronic (0 to 6 month)
Cognitive function
Assessed via a validated cognitive test battery.
Measured: Chronic (0 to 6 month)
Liver fat and blood flow assessment
Assessment via 3T MRI in a sub-group of participants.
Measured: Chronic (0 to 6 month)
Bio-availability
Flavonoid and metabolite levels will be assessed in blood and 24 hour urine samples.
Measured: Chronic (0 to 6 month)
Metabolite phenotype effects
The gut microbiome will be assessed from faecal sample collection and the impact on metabolism and of genotype, will be assessed via a targeted approach.
Measured: Chronic (0 to 6 month)
Acute +24 hour effect of single (26g) intervention intake, given with high fat challenge
Insulin resistance, lipaemia, vascular, cognitive and lung function measured pre- and post-intervention in combination with a high fat challenge in a sub-group of participants. Urine samples and blood samples (over a 24 hour period) will be taken for biomarker analysis.
Measured: Chronic (0 to 6 month)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2014 (estimated)
- Study startJan 2014
- Primary completion7 Nov 2016
- Study completion7 Nov 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Insulin ResistanceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 144 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of East Anglia
- Sponsor type
- University, hospital or other
- Collaborators
- Harvard School of Public Health (HSPH)
- Responsible party
- Sponsor
- Investigators
- Aedin Cassidy, PhD, Principal investigator, University of East Anglia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02035592
- Sponsor's protocol ID
- R21478-C
- Acronym
- CIRCLES
- Status last verified
- Jan 2017
- First submitted
- 10 Jan 2014
- Last updated
- 29 Sep 2017
- Results posted
- No
- Data monitoring committee
- No
Publications
Curtis PJ, van der Velpen V, Berends L, Jennings A, Haag L, Minihane AM, Chandra P, Kay CD, Rimm EB, Cassidy A. Chronic and postprandial effect of blueberries on cognitive function, alertness, and mood in participants with metabolic syndrome - results from a six-month, double-blind, randomized controlled trial. Am J Clin Nutr. 2024 Mar;119(3):658-668. doi: 10.1016/j.ajcnut.2023.12.006. Epub 2024 Feb 6.
PubMed 38432713Curtis PJ, Berends L, van der Velpen V, Jennings A, Haag L, Chandra P, Kay CD, Rimm EB, Cassidy A. Blueberry anthocyanin intake attenuates the postprandial cardiometabolic effect of an energy-dense food challenge: Results from a double blind, randomized controlled trial in metabolic syndrome participants. Clin Nutr. 2022 Jan;41(1):165-176. doi: 10.1016/j.clnu.2021.11.030. Epub 2021 Nov 27.
PubMed 34883305Curtis PJ, van der Velpen V, Berends L, Jennings A, Feelisch M, Umpleby AM, Evans M, Fernandez BO, Meiss MS, Minnion M, Potter J, Minihane AM, Kay CD, Rimm EB, Cassidy A. Blueberries improve biomarkers of cardiometabolic function in participants with metabolic syndrome-results from a 6-month, double-blind, randomized controlled trial. Am J Clin Nutr. 2019 Jun 1;109(6):1535-1545. doi: 10.1093/ajcn/nqy380.
PubMed 31136659
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effects of Blueberry Anthocyanins on Insulin Resistance and Vascular, Lung and Cognitive Function in a Population With Metabolic Syndrome.
- ClinicalTrials.gov ID
- NCT02035592
- Acronym / sponsor ID
- CIRCLES / R21478-C
- Conditions
- Insulin Resistance, Metabolic Syndrome X
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 144 participants (estimated)
- Lead sponsor
- University of East AngliaUniversity, hospital or other
- Collaborators
- Harvard School of Public Health (HSPH)
- Study start
- Jan 2014
- Primary completion
- 7 Nov 2016 (actual)
- Study completion
- 7 Nov 2016 (actual)
- First posted
- 14 Jan 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the dose-dependent impact of 6 month freeze-dried blueberry powder intake on insulin sensitivity and resistance, cardiovascular disease risk factors, and lung and cognitive function in overweight and obese participants with metabolic syndrome. We will also examine acute post-prandial effects of blueberry intake (at baseline and at 6-months).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Full dose blueberry | Active comparator | Other: Full dose blueberry26g of freeze dried blueberry powder; equivalent to 2 portions of fresh blueberries per day. Frequency: 26g per day. Total duration: 6-month. |
| Half dose blueberry | Active comparator | Other: Half dose blueberry26g of freeze dried powder; containing 13g of freeze dried blueberry powder and 13g of placebo comparator material; equivalent to 1 portion of fresh blueberries per day. Frequency: 26g per day. Total duration: 6-month. |
| Control | Placebo comparator | Other: ControlMatched control powder; matched for appearance, taste and sugar content. Frequency: 26g per day. Total duration: 6-month. |
Who may qualify
- Ages
- 50 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Men and postmenopausal women (≥ 1 year since last menstruation)
- 50 to 75 years old
- BMI of ≥ 25 kg/m2
- 3 characteristics of metabolic syndrome i.e: Waist circumference ≥ 102 cm for men, ≥ 88 cm for women; Triglycerides ≥ 1.7 mmol/L (or drug treatment for elevated triglycerides); HDL-cholesterol < 1.0 mmol/L for men, < 1.3 mmol/L for women (or drug treatment for low HDL-cholesterol); Blood pressure ≥ 130 mm Hg systolic and/or ≥ 85 mm Hg diastolic blood pressure; Fasting blood glucose ≥ 5.56 mmol/L
- Successful biochemical, haematological and urinalysis assessment at screening
Key exclusion criteria (10 listed)
- Current smokers, or ex-smokers ceasing < 6 months ago
- Existing or significant past medical history of vascular disease or medical conditions likely to affect the study measures
- Fructose intolerance or known allergies to the intervention treatments
- On therapeutic diets or having experienced substantial weight loss within 3 months of screening
- Taking flavonoid containing supplements (and unwilling to cease intake during, and 1 month preceding the trial)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Full dose blueberryFull dose: 26g of freeze dried blueberry powder to be incorporated into the habitual diet. Dietary restrictions will be observed (i.e. avoidance of blueberry, and restricted intake of anthocyanin rich foods) for 21 days prior to the first assessment visit and throughout the study. | Other | Full dose blueberry |
| Half dose blueberryHalf dose: 26g of freeze dried powder (containing 13g of freeze dried blueberry powder and 13g of placebo comparator material) to be incorporated into the habitual diet. Dietary restrictions will be observed (i.e. avoidance of blueberry, and restricted intake of anthocyanin rich foods) for 21 days prior to the first assessment visit and throughout the study. | Other | Half dose blueberry |
| ControlControl: 26g of placebo comparator material to be incorporated into the habitual diet. Dietary restrictions will be observed (i.e. avoidance of blueberry, and restricted intake of anthocyanin rich foods) for 21 days prior to the first assessment visit and throughout the study. | Other | Control |
Primary outcome
Insulin resistance
Time frame: Chronic (0 to 6 month)
Assessed, in the fasted state, via HOMA-IR calculation in all participants; indirect assessment.
8 secondary outcomes
Insulin resistance
Time frame: Chronic (0 to 6 month)
Blood pressure and blood vessel regulation
Time frame: Chronic (0 to 6 month)
Lung function
Time frame: Chronic (0 to 6 month)
Cognitive function
Time frame: Chronic (0 to 6 month)
Liver fat and blood flow assessment
Time frame: Chronic (0 to 6 month)
Bio-availability
Time frame: Chronic (0 to 6 month)
Metabolite phenotype effects
Time frame: Chronic (0 to 6 month)
Acute +24 hour effect of single (26g) intervention intake, given with high fat challenge
Time frame: Chronic (0 to 6 month)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2017.
- Derived from this study: PubMed 38432713Curtis PJ, van der Velpen V, Berends L, Jennings A, Haag L, Minihane AM, Chandra P, Kay CD, Rimm EB, Cassidy A. Chronic and postprandial effect of blueberries on cognitive function, alertness, and mood in participants with metabolic syndrome - results from a six-month, double-blind, randomized controlled trial. Am J Clin Nutr. 2024 Mar;119(3):658-668. doi: 10.1016/j.ajcnut.2023.12.006. Epub 2024 Feb 6.
- Derived from this study: PubMed 34883305Curtis PJ, Berends L, van der Velpen V, Jennings A, Haag L, Chandra P, Kay CD, Rimm EB, Cassidy A. Blueberry anthocyanin intake attenuates the postprandial cardiometabolic effect of an energy-dense food challenge: Results from a double blind, randomized controlled trial in metabolic syndrome participants. Clin Nutr. 2022 Jan;41(1):165-176. doi: 10.1016/j.clnu.2021.11.030. Epub 2021 Nov 27.
- Derived from this study: PubMed 31136659Curtis PJ, van der Velpen V, Berends L, Jennings A, Feelisch M, Umpleby AM, Evans M, Fernandez BO, Meiss MS, Minnion M, Potter J, Minihane AM, Kay CD, Rimm EB, Cassidy A. Blueberries improve biomarkers of cardiometabolic function in participants with metabolic syndrome-results from a 6-month, double-blind, randomized controlled trial. Am J Clin Nutr. 2019 Jun 1;109(6):1535-1545. doi: 10.1093/ajcn/nqy380.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Aedin Cassidy, PhD principal investigator
University of East Anglia
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Full dose blueberry and Half dose blueberry in people with Insulin Resistance and Metabolic Syndrome X, run by University of East Anglia at 4 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United Kingdom, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insulin resistance (time frame: Chronic (0 to 6 month)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02035592, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Sep 2017.