Trial Outcomes & Findings for A Single Supplement of a Standardised Bilberry Extract Modifies Glycaemic Response (NCT NCT01245270)

Results Overview

Volunteers were fasted (10-12 h) overnight before the OGTT. Venous blood samples were taken through an indwelling cannula inserted into a forearm vein at -15, -10 and -5 (fasted) and at 15, 30, 45, 60, 90, 120, 150 and 300 min after consuming 75 g of Polycal liquid (carbohydrate, 61·9%; polysaccharide, 49·2 %; sugars, 12·2%; glucose, 0·6%; maltose, 11·6%; http://www. nutricia.co.uk). Polycal was selected as the main carbohydrate as it is in the form of polysaccharides and this is closer to normal dietary consumption than glucose only.The volunteers consumed the appropriate capsule (0 min), glucose load and a further sample of water (70 ml) within 3 min. For those volunteers taking the control capsule, additional sugar (fructose and dextrose/glucose) was added double-blinded to the water to match the free sugar content of the Mirtoselect® capsules. Movement during the 300 min OGTT was kept to a minimum.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

8 participants

Primary outcome timeframe

Plasma was collected at -15, -10 and -5 (fasted) and at 15, 30, 45, 60, 90, 120, 150 and 300 min post capsule

Results posted on

2021-03-10

Participant Flow

Eight male volunteer subjects with T2D controlled by diet and lifestyle alone or with impaired glucose tolerance were recruited from the Aberdeen area of the UK. Subjects were only included if they were not on any special religious or prescribed diet and had a stable weight.

Participant milestones

Participant milestones
Measure	Single Control Capsule First Then Bilberry Capsule In a cross-over design, volunteers (n 8) were randomised and double-blinded into two groups matched for BMI as well as age and given a single capsule of either 0·47 g of Mirtoselect® (a standardised bilberry extract (36 % (w/w) anthocyanins)) which equates to about 50 g of fresh bilberries formulated in gelatin capsules or a control capsule consisting of microcrystalline cellulose in an opaque gelatin capsule, followed by oral glucose tolerance testing (OGTT). The reverse procedure was conducted following a 2-week washout period. The volunteers were asked to consume a low-phytochemical diet 3 d before taking the capsule and for the 24 h after taking the capsule on both occasions. In addition the volunteers were asked to record what they ate over the same period in a food diary to ensure that they adhered to the low-phytochemical diet. Subjects were reimbursed travelling expenses on completion of the study.	Single Bilberry Capsule First Then Control Capsule In a cross-over design, volunteers (n 8) were randomised and double-blinded into two groups matched for BMI as well as age and given a single capsule of either 0·47 g of Mirtoselect® (a standardised bilberry extract (36 % (w/w) anthocyanins)) which equates to about 50 g of fresh bilberries formulated in gelatin capsules or a control capsule consisting of microcrystalline cellulose in an opaque gelatin capsule, followed by oral glucose tolerance testing (OGTT). The reverse procedure was conducted following a 2-week washout period. The volunteers were asked to consume a low-phytochemical diet 3 d before taking the capsule and for the 24 h after taking the capsule on both occasions. In addition the volunteers were asked to record what they ate over the same period in a food diary to ensure that they adhered to the low-phytochemical diet. Subjects were reimbursed travelling expenses on completion of the study.
Overall Study STARTED	4	4
Overall Study COMPLETED	4	4
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Single Supplement of a Standardised Bilberry Extract Modifies Glycaemic Response

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Bilberry Capsule First, Then Control Capsule n=4 Participants In a cross-over design, eight volunteers were randomised and double-blinded into two groups matched for BMI as well as age and given a single capsule of either 0·47 g of Mirtoselect® (a standardised bilberry extract (36 % (w/w) anthocyanins)) which equates to about 50 g of fresh bilberries formulated in gelatin capsules or a control capsule consisting of microcrystalline cellulose in an opaque gelatin capsule, followed by oral glucose tolerance testing (OGTT). The reverse procedure was conducted following a 2-week washout period. The volunteers were asked to consume a low-phytochemical diet 3 d before taking the capsule and for the 24 h after taking the capsule on both occasions. In addition the volunteers were asked to record what they ate over the same period in a food diary to ensure that they adhered to the low-phytochemical diet. Subjects were reimbursed travelling expenses on completion of the study.	Control Capsule First, Then Bilberry Capsule n=4 Participants In a cross-over design, eight volunteers were randomised and double-blinded into two groups matched for BMI as well as age and given a single capsule of either 0·47 g of Mirtoselect® (a standardised bilberry extract (36 % (w/w) anthocyanins)) which equates to about 50 g of fresh bilberries formulated in gelatin capsules or a control capsule consisting of microcrystalline cellulose in an opaque gelatin capsule, followed by oral glucose tolerance testing (OGTT). The reverse procedure was conducted following a 2-week washout period. The volunteers were asked to consume a low-phytochemical diet 3 d before taking the capsule and for the 24 h after taking the capsule on both occasions. In addition the volunteers were asked to record what they ate over the same period in a food diary to ensure that they adhered to the low-phytochemical diet. Subjects were reimbursed travelling expenses on completion of the study.	Total n=8 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	62 years STANDARD_DEVIATION 5 • n=5 Participants	62 years STANDARD_DEVIATION 5 • n=7 Participants	62 years STANDARD_DEVIATION 5 • n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Region of Enrollment United Kingdom	4 participants n=5 Participants	4 participants n=7 Participants	8 participants n=5 Participants
BMI	30 Kg/m2 STANDARD_DEVIATION 4 • n=5 Participants	30 Kg/m2 STANDARD_DEVIATION 4 • n=7 Participants	30 Kg/m2 STANDARD_DEVIATION 4 • n=5 Participants

PRIMARY outcome

Timeframe: Plasma was collected at -15, -10 and -5 (fasted) and at 15, 30, 45, 60, 90, 120, 150 and 300 min post capsule

Volunteers were fasted (10-12 h) overnight before the OGTT. Venous blood samples were taken through an indwelling cannula inserted into a forearm vein at -15, -10 and -5 (fasted) and at 15, 30, 45, 60, 90, 120, 150 and 300 min after consuming 75 g of Polycal liquid (carbohydrate, 61·9%; polysaccharide, 49·2 %; sugars, 12·2%; glucose, 0·6%; maltose, 11·6%; http://www. nutricia.co.uk). Polycal was selected as the main carbohydrate as it is in the form of polysaccharides and this is closer to normal dietary consumption than glucose only.The volunteers consumed the appropriate capsule (0 min), glucose load and a further sample of water (70 ml) within 3 min. For those volunteers taking the control capsule, additional sugar (fructose and dextrose/glucose) was added double-blinded to the water to match the free sugar content of the Mirtoselect® capsules. Movement during the 300 min OGTT was kept to a minimum.

Outcome measures

Outcome measures
Measure	Single Placebo Capsule n=8 Participants In a cross-over design, volunteers (n 8) were randomised and double-blinded into two groups matched for BMI as well as age and given a single capsule of either 0·47 g of Mirtoselect® (a standardised bilberry extract (36 % (w/w) anthocyanins)) which equates to about 50 g of fresh bilberries formulated in gelatin capsules or a control capsule consisting of microcrystalline cellulose in an opaque gelatin capsule, followed by oral glucose tolerance testing (OGTT). The reverse procedure was conducted following a 2-week washout period. The volunteers were asked to consume a low-phytochemical diet 3 d before taking the capsule and for the 24 h after taking the capsule on both occasions. In addition the volunteers were asked to record what they ate over the same period in a food diary to ensure that they adhered to the low-phytochemical diet. Subjects were reimbursed travelling expenses on completion of the study.	Single Blaeberry Capsule n=8 Participants In a cross-over design, volunteers (n 8) were randomised and double-blinded into two groups matched for BMI as well as age and given a single capsule of either 0·47 g of Mirtoselect® (a standardised bilberry extract (36 % (w/w) anthocyanins)) which equates to about 50 g of fresh bilberries formulated in gelatin capsules or a control capsule consisting of microcrystalline cellulose in an opaque gelatin capsule, followed by oral glucose tolerance testing (OGTT). The reverse procedure was conducted following a 2-week washout period. The volunteers were asked to consume a low-phytochemical diet 3 d before taking the capsule and for the 24 h after taking the capsule on both occasions. In addition the volunteers were asked to record what they ate over the same period in a food diary to ensure that they adhered to the low-phytochemical diet. Subjects were reimbursed travelling expenses on completion of the study.
Plasma Glucose iAUC (Incremental Area Under the Curve; mM*Min)	836 glucose iAUC (mM*min) Standard Error 97	693 glucose iAUC (mM*min) Standard Error 103

PRIMARY outcome

Timeframe: Plasma was collected at -15, -10 and -5 (fasted) and at 15, 30, 45, 60, 90, 120, 150 and 300 min after the capsule

Volunteers were fasted (10-12 h) overnight before the OGTT. Venous blood samples were taken through an indwelling cannula inserted into a forearm vein at -15, -10 and -5 (fasted) and at 15, 30, 45, 60, 90, 120, 150 and 300 min after consuming 75 g of Polycal liquid (carbohydrate, 61•9%; polysaccharide, 49•2 %; sugars, 12•2%; glucose, 0•6%; maltose, 11•6%; http://www. nutricia.co.uk). Polycal was selected as the main carbohydrate as it is in the form of polysaccharides and this is closer to normal dietary consumption than glucose only.The volunteers consumed the appropriate capsule (0 min), glucose load and a further sample of water (70 ml) within 3 min. For those volunteers taking the control capsule, additional sugar (fructose and dextrose/glucose) was added double-blinded to the water to match the free sugar content of the Mirtoselect® capsules. Movement during the 300 min OGTT was kept to a minimum.

Outcome measures

Outcome measures
Measure	Single Placebo Capsule n=8 Participants In a cross-over design, volunteers (n 8) were randomised and double-blinded into two groups matched for BMI as well as age and given a single capsule of either 0·47 g of Mirtoselect® (a standardised bilberry extract (36 % (w/w) anthocyanins)) which equates to about 50 g of fresh bilberries formulated in gelatin capsules or a control capsule consisting of microcrystalline cellulose in an opaque gelatin capsule, followed by oral glucose tolerance testing (OGTT). The reverse procedure was conducted following a 2-week washout period. The volunteers were asked to consume a low-phytochemical diet 3 d before taking the capsule and for the 24 h after taking the capsule on both occasions. In addition the volunteers were asked to record what they ate over the same period in a food diary to ensure that they adhered to the low-phytochemical diet. Subjects were reimbursed travelling expenses on completion of the study.	Single Blaeberry Capsule n=8 Participants In a cross-over design, volunteers (n 8) were randomised and double-blinded into two groups matched for BMI as well as age and given a single capsule of either 0·47 g of Mirtoselect® (a standardised bilberry extract (36 % (w/w) anthocyanins)) which equates to about 50 g of fresh bilberries formulated in gelatin capsules or a control capsule consisting of microcrystalline cellulose in an opaque gelatin capsule, followed by oral glucose tolerance testing (OGTT). The reverse procedure was conducted following a 2-week washout period. The volunteers were asked to consume a low-phytochemical diet 3 d before taking the capsule and for the 24 h after taking the capsule on both occasions. In addition the volunteers were asked to record what they ate over the same period in a food diary to ensure that they adhered to the low-phytochemical diet. Subjects were reimbursed travelling expenses on completion of the study.
Plasma Insulin iAUC (Incremental Area Under the Curve; ng/ml*Min)	358 insulin iAUC (ng/ml*min) Standard Error 131	294 insulin iAUC (ng/ml*min) Standard Error 113

SECONDARY outcome

Timeframe: Plasma will also be collected -15,-10, -5, 15, 30, 45, 60, 90, 120, 150, and 300 minutes and 24 hours post intervention

To measure the amount of anthocyanins and phenolic-derived metabolites by liquid chromatography mass spectrometry (LC-MS) being absorbed from the gut and excreted following the single intervention.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Urine will also be collected (if possible) 0, 1, 3 and 5 hours, with all urine collected within the 24 hour time period post intervention

To measure the amount of anthocyanins and phenolic-derived metabolites by liquid chromatography mass spectrometry (LC-MS) being absorbed from the gut and excreted following the single intervention.

Outcome measures

Outcome data not reported

Adverse Events

Single Bilberry Capsule

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Single Placebo Capsule

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr Nigel Hoggard

University of Aberdeen Rowett Institute of Nutrition and Health

Phone: [+44] (0) 1224 438700

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place