PROGRAIN2: Phenolic-rich Oats and Artery Improvement

• Sponsor: University of Reading (Other)
• Overall Status: Completed
• CT.gov ID: NCT02731755
• Collaborator: Biotechnology and Biological Sciences Research Council (Other), Rothamsted Research (Other), PepsiCo Global R&D (Industry), University of Roehampton (Other)
• Enrollment: 18
• Locations: 2
• Arms: 2
• Actual Duration (Months): 10
• Patients Per Site: 9
• Patients Per Site Per Month: 0.9

Study Details

Study Description

Brief Summary

In this proposed human trial, the investigators aim to establish whether consumption of one portion of phenolic acid-rich oats leads to acute improvements (i.e. 1-24h post-intake) in markers of cardiovascular disease risk relative to an energy matched control intervention in healthy men with high-normal to mildly elevated blood pressure.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Other: Oat; Other: Control	N/A

Detailed Description

A diet rich in whole grain is inversely associated with cardiovascular disease risk. Whole grains contain a wide range dietary components including potentially vasoactive phenolic acids.

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Acute Cardiovascular Effects of Phenolic Rich Oats in Men With Above Average Blood Pressure
• Actual Study Start Date: Jan 1, 2016
• Actual Primary Completion Date: Nov 1, 2016
• Actual Study Completion Date: Nov 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Oat intervention 67.7g oatflake and 22.5g oatbran concentrate - single intake (mixed with water)	Other: Oat; The study oat intervention products will consist of 67.7g oatflake and 22.5g oatbran concentrate.
Placebo Comparator: Control 39.4g cream of rice, 6.1g sunflower oil, 29.5g skimmed milk, 5.6g pectin powder, 6.5g cellulose and mixed with water	Other: Control; 60g cream of rice

Outcome Measures

Primary Outcome Measures

1. Flow Mediated Dilatation [1 hour, 6 hours and 24 hours]

   Technique to assess the flexibility of the endothelium in larger peripheral blood vessels

Secondary Outcome Measures

1. Laser Doppler Iontophoresis [Baseline(BL), 2hours and 24hours]

   Acute postprandial timecourse from Baseline to 2 hours, 24hours, AUC - area under the blood flow and time curve Ach-iAUC-endothelium dependent incremental area under the curve SNP-iAUC-endothelium independent incremental area under the curve Ach-AUC- endothelium dependent area under the curve

2. Phenolic Acids Metabolites - Ferulic Acid [Baseline, 1hour, 2 hours and 24hours]

   Concentration of phenolic acid metabolites in plasma and urine as Assessed by liquid chromatography/mass spectrometry magnitude of increase from Baseline to 24h

3. Plasma Nitric Oxide Analysis [Acute postprandial timecourse from Baseline, 1hour to 24hours.]

   Concentration of nitric oxide in nmol

4. NADPH Oxidase Activity in Neutrophil Blood Cells [Baseline, 2 hours and 24 hours]

   NADPH oxidase activity will be calculated as the difference between values obtained in PMA The fluorescence intensity was measured by C6 Flow Cytometer

5. Plasma Glucose [Acute postprandial timecourse from Baseline, 1hour to 24hours.]

   Glucose concentration in mmol/L

6. Plasma Insulin [Acute postprandial timecourse from Baseline, 1hour to 24hours.]

   Insulin concentration in pmol/L

7. Renin Activity [Acute postprandial timecourse from Baseline, 1hour to 24hours.]

   Renin activity in ng/(mL*hour)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 25 Years to 75 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Above average blood pressure (i.e. systolic 120-159 mmHg and diastolic 75-99 mmHg)

Exclusion Criteria:

• Abnormal biochemical, haematological results as assessed at health screening

• Hypertension (i.e. systolic/diastolic blood pressure ≥160/100 mm Hg) BMI >35

• Current smoker or ex-smoker ceasing <3 months ago

• Past or existing medical history of vascular disease, diabetes, hepatic, renal, gastrointestinal, haematological, neurological, thyroidal disease or cancer

• Prescribed or taking lipid lowering, antihypertensive, vasoactive (e.g. Viagra), anti-inflammatory, antibiotic or antidepressant medication

• Allergies to whole grains

• Parallel participation in another research project

• Having flu vaccination or antibiotics within 3 months of trial start

• On a weight reduction regime or taking food supplements within 3 months of trial start

• Performing high level of physical activity (i.e. >3 x 20 min aerobic exercise/week)

• Consumption of ≥21 units of alcohol/week

• Small veins not allowing cannulation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hugh Sinclair Unit of Human Nutrition	Reading	Berkshire	United Kingdom	RG6 6AP
2	Hugh Sinclair Unit of Human Nutrition	Reading		United Kingdom	RG66AP

Sponsors and Collaborators

• University of Reading
• Biotechnology and Biological Sciences Research Council
• Rothamsted Research
• PepsiCo Global R&D
• University of Roehampton

Investigators

• Principal Investigator: Jeremy P Spencer, Professor, University of Reading

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jeremy Paul Edward Spencer, Professor, University of Reading
• ClinicalTrials.gov Identifier: NCT02731755
• Other Study ID Numbers: PROGRAIN2
• First Posted: Apr 8, 2016
• Last Update Posted: Nov 1, 2019
• Last Verified: Oct 1, 2019

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Jeremy Paul Edward Spencer, Professor, University of Reading: Oats; Phenolic acid; FMD; LDI; Avenanthramide

Study Results

Participant Flow

Arm/Group Title	Oat Then Control	Control Then Oat
Arm/Group Description	The first intervention is oat, the second intervention is control	The first intervention is control, the second intervention is oat
Period Title: First Intervention
STARTED	8	10
COMPLETED	8	8
NOT COMPLETED	0	2
Period Title: First Intervention
STARTED	8	8
COMPLETED	8	8
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	All Participant
Arm/Group Description	Crossover study - All participant
Overall Participants	16
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47 (4)
Sex: Female, Male (Count of Participants)
Female	0 0%
Male	16 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	16 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United Kingdom	16 100%
Systolic blood pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	133.9 (2.2)
Diastolic blood pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	81.1 (1.0)

Outcome Measures

1. Primary Outcome

Title	Flow Mediated Dilatation
Description	Technique to assess the flexibility of the endothelium in larger peripheral blood vessels
Time Frame	1 hour, 6 hours and 24 hours

Outcome Measure Data

Analysis Population Description

Excluded data from 2 volunteers as their results were out of the normal range

Arm/Group Title	Oat Intervention	Control
Arm/Group Description	The first intervention is oat, the second intervention is control	The first intervention is control, the second intervention is oat
Measure Participants	14	14
1h	4.4 (0.7)	3.9 (0.9)
6h	3.4 (0.6)	4.4 (0.8)
24h	4.4 (0.4)	3.6 (0.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oat Intervention, Control
	Comments	Between time points and treatments, calculated p value
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5
	Comments
	Method	Mixed Models Analysis
	Comments

2. Secondary Outcome

Title	Laser Doppler Iontophoresis
Description	Acute postprandial timecourse from Baseline to 2 hours, 24hours, AUC - area under the blood flow and time curve Ach-iAUC-endothelium dependent incremental area under the curve SNP-iAUC-endothelium independent incremental area under the curve Ach-AUC- endothelium dependent area under the curve
Time Frame	Baseline(BL), 2hours and 24hours

Outcome Measure Data

Analysis Population Description

Excluded data from 2 volunteers as their results were out of the normal range

Arm/Group Title	Oat Intervention	Control
Arm/Group Description	The first intervention is oat, the second intervention is control	The first intervention is control, the second intervention is oat
Measure Participants	14	14
Ach-i AUC, BL	538.2 (90.4)	465 (70.6)
Ach-i AUC, 2h	681.8 (182)	463.7 (55.4)
Ach-i AUC, 24h	381.3 (61.4)	315 (45.5)
SNP-iAUC BL	661.1 (52.4)	757.1 (43.2)
SNP-iAUC 2h	709.4 (68.4)	502.9 (25.6)
SNP-iAUC,24h	622.4 (50.6)	513.7 (35.8)
Ach-AUC, BL	1593.9 (198.9)	1534.1 (144.2)
Ach-AUC, 2h	1678.3 (140.6)	1358.3 (116.9)
Ach-AUC, 24h	1560.9 (161.3)	1701.6 (190.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oat Intervention, Control
	Comments	Ach-iAUC
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.04
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Oat Intervention, Control
	Comments	SNP-IAUC
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.007
	Comments
	Method	Mixed Models Analysis
	Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Oat Intervention, Control
	Comments	Ach - AUC
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Mixed Models Analysis
	Comments

3. Secondary Outcome

Title	Phenolic Acids Metabolites - Ferulic Acid
Description	Concentration of phenolic acid metabolites in plasma and urine as Assessed by liquid chromatography/mass spectrometry magnitude of increase from Baseline to 24h
Time Frame	Baseline, 1hour, 2 hours and 24hours

Outcome Measure Data

Analysis Population Description

Excluded data from 2 volunteers as their results were out of the normal range

Arm/Group Title	Oat Intervention	Control
Arm/Group Description	The first intervention is oat, the second intervention is control	The first intervention is control, the second intervention is oat
Measure Participants	14	14
BL	10.6 (7.8)	0.4 (2.4)
1h	33.9 (17.5)	9 (6.4)
2h	153.5 (145.2)	10.3 (9.3)
24h	373 (4)	222 (24)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oat Intervention, Control
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9
	Comments
	Method	Mixed Models Analysis
	Comments

4. Secondary Outcome

Title	Plasma Nitric Oxide Analysis
Description	Concentration of nitric oxide in nmol
Time Frame	Acute postprandial timecourse from Baseline, 1hour to 24hours.

Outcome Measure Data

Analysis Population Description

No data collected

Arm/Group Title	Oat Intervention	Control
Arm/Group Description	The first intervention is oat, the second intervention is control	The first intervention is control, the second intervention is oat
Measure Participants	0	0

5. Secondary Outcome

Title	NADPH Oxidase Activity in Neutrophil Blood Cells
Description	NADPH oxidase activity will be calculated as the difference between values obtained in PMA The fluorescence intensity was measured by C6 Flow Cytometer
Time Frame	Baseline, 2 hours and 24 hours

Outcome Measure Data

Analysis Population Description

Excluded data from 2 volunteers as their results were out of the normal range

Arm/Group Title	Oat Intervention	Control
Arm/Group Description	The first intervention is oat, the second intervention is control	The first intervention is control, the second intervention is oat
Measure Participants	14	14
BL	55.7 (7)	58.6 (8)
2h	43.6 (5)	47.9 (8)
24h	63.6 (6)	61.6 (9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Oat Intervention, Control
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7
	Comments
	Method	Mixed Models Analysis
	Comments

6. Secondary Outcome

Title	Plasma Glucose
Description	Glucose concentration in mmol/L
Time Frame	Acute postprandial timecourse from Baseline, 1hour to 24hours.

Outcome Measure Data

Analysis Population Description

Data not collected

Arm/Group Title	Oat Intervention	Control
Arm/Group Description	The first intervention is oat, the second intervention is control	The first intervention is control, the second intervention is oat
Measure Participants	0	0

7. Secondary Outcome

Title	Plasma Insulin
Description	Insulin concentration in pmol/L
Time Frame	Acute postprandial timecourse from Baseline, 1hour to 24hours.

Outcome Measure Data

Analysis Population Description

Data not collected

Arm/Group Title	Oat Intervention	Control
Arm/Group Description	The first intervention is oat, the second intervention is control	The first intervention is control, the second intervention is oat
Measure Participants	0	0

8. Secondary Outcome

Title	Renin Activity
Description	Renin activity in ng/(mL*hour)
Time Frame	Acute postprandial timecourse from Baseline, 1hour to 24hours.

Outcome Measure Data

Analysis Population Description

Data not collected

Arm/Group Title	Oat Intervention	Control
Arm/Group Description	The first intervention is oat, the second intervention is control	The first intervention is control, the second intervention is oat
Measure Participants	0	0

Adverse Events

Time Frame	2 months
Arm/Group Title	Oat Intervention		Control
Arm/Group Description	Participants received oat intervention		Participants received control intervention
All Cause Mortality
	Oat Intervention		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/18 (0%)
Serious Adverse Events
	Oat Intervention		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/18 (0%)		0/18 (0%)
Other (Not Including Serious) Adverse Events
	Oat Intervention		Control
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/18 (5.6%)		0/18 (0%)
Nervous system disorders
Faint	1/18 (5.6%)	1	0/18 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.