DIVAS: Dietary Intervention and Vascular Function

• Sponsor: University of Reading (Other)
• Overall Status: Completed
• CT.gov ID: NCT01478958
• Collaborator: (none)
• Enrollment: 202
• Locations: 2
• Arms: 3
• Duration (Months): 29
• Patients Per Site: 101
• Patients Per Site Per Month: 3.5

Study Details

Study Description

Brief Summary

It is well established that diet plays an important role in both the development and progression of heart disease. Different types of dietary fat have varying effects on heart disease risk factors. The elasticity of an individual's blood vessels is strongly associated with heart disease risk and recent evidence suggests that dietary manipulation may influence elasticity of the blood vessels with dietary fat (including saturated, monounsaturated and polyunsaturated fatty acids) as a potentially important modulator. Substantial evidence exists on the effects of monounsaturated fats (type of fatty acids mainly found in olive and rapeseed oil), n-6 polyunsaturated fats (type of polyunsaturated fatty acids found in vegetable oils) and saturated fat (found mainly in animal derived products) on lipid levels. However, the influence of these dietary fats on the elasticity of blood vessels remains unclear.The main purpose of the DIVAS study is to determine the effects of the substitution of saturated fats with either n-6 polyunsaturated or monounsaturated fats on blood vessel elasticity and to determine the effects of these different dietary fats on other risk factors for heart disease including lipoproteins and inflammatory biomarkers.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Disease	Dietary Supplement: SFA diet; Dietary Supplement: MUFA diet; Dietary Supplement: n-6 PUFA diet	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 202 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Prevention
• Official Title: The Effects of the Substitution of Dietary SFA With n-6 PUFA or MUFA on Vascular Function
• Study Start Date: May 1, 2010
• Actual Primary Completion Date: Oct 1, 2012
• Actual Study Completion Date: Oct 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: high saturated fat diet	Dietary Supplement: SFA diet; Volunteers are following a high saturated fat diet for a 4-month period
Experimental: high monounsaturated fat diet	Dietary Supplement: MUFA diet; Volunteers are following a high monounsaturated fat diet for a 4-month period
Experimental: high n-6 polyunsaturated fat diet	Dietary Supplement: n-6 PUFA diet; Volunteers are following a high n-6 polyunsaturated fat diet for a 4-month period

Outcome Measures

Primary Outcome Measures

1. Percent Change in Flow Mediated Dilatation (FMD) [Baseline, 4 months]

Secondary Outcome Measures

1. Cardiovascular Risk Factors (Lipids, Inflammatory Markers, Indices of Insulin Resistance, Cell Microparticles, Endothelial Progenitor Cells) [4 months]

   Data for fasting serum lipids (total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), TC:HDL-C ratio, low-density lipoprotein cholesterol (LDL-C), triacylglycerol (TAG)).

2. 24-hour Ambulatory Blood Pressure [4 months]

   24-hour, daytime and night-time measures of systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP; SBP-DBP) and heart rate (HR)

3. Vascular Stiffness by Pulse Wave Velocity (PWV), Pulse Wave Analysis (PWA) and Digital Volume Pulse (DVP) [4 months]

   PWV (m/s) PWA produces Augmentation Index (AIx; %) DVP produces Stiffness Index (SI; m/s) and Reflection Index (RI; %)

4. Microvascular Reactivity (Laser Doppler Imaging With Iontophoresis) [4 months]

   Laser Doppler imaging (LDI) with iontophoresis of acetylcholine (Ach; endothelium-dependent vasodilation) and sodium nitroprusside (SNP; endothelium-independent vasodilation).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

Adults should have a relative risk (RR) of > 1.5 of developing cardiovascular disease (CVD) based on presenting with at least one recognised risk factor for CVD:

• total cholesterol (TC) > 6.0 mmol/l

• HDL cholesterol (HDLC) ≤ 1.0 mmol/l male, ≤ 1.3 mmol/l female

• Glucose ≥ 6 mmol/l

• Stage 1 hypertension or above i.e. a systolic BP ≥ 140 mmHg, diastolic BP ≥ 90 mmHg

• BMI 28-35 kg/m2

• waist >102 cm male or > 84 cm female

• Adults with a first degree relative with either a history of premature CVD - age of onset younger than 55 y in fathers, sons or brothers or younger than 65 y in mothers, daughters or sisters, or type 2 diabetes.

Exclusion Criteria:

• having suffered a myocardial infarction/stroke in the past 12 months

• diabetic (diagnosed or fasting glucose > 7 mmol/l) or suffer from other endocrine disorders

• suffering from renal or bowel disease or have a history of choleostatic liver or pancreatitis

• on drug treatment for hyperlipidaemia, hypertension, inflammation or hypercoagulation

• no history of alcohol abuse

• planning or on a weight reducing regime

• taking any fish oil, fatty acid or vitamin and mineral supplements

• pregnant, lactating or planning a pregnancy

• smokers

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Food and Nutritional Sciences, University of Reading	Reading	Berkshire	United Kingdom	RG6 6AP
2	University of Reading	Reading	Berkshire	United Kingdom	RG6 6AP

Sponsors and Collaborators

• University of Reading

Investigators

• Principal Investigator: Julie A Lovegrove, BSc PhD RNutr, University of Reading

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Julie Lovegrove, Professor, University of Reading
• ClinicalTrials.gov Identifier: NCT01478958
• Other Study ID Numbers: N02044
• First Posted: Nov 23, 2011
• Last Update Posted: Jul 15, 2014
• Last Verified: Jun 1, 2014

• Keywords provided by Julie Lovegrove, Professor, University of Reading: fatty acids; cardiovascular disease; vascular function; microparticles
• Additional relevant MeSH terms: Cardiovascular Diseases

Study Results

Participant Flow

Recruitment Details	Recruited in three cohorts between November 2009 and June 2012.

Arm/Group Title	High Saturated Fat Diet	High Monounsaturated Fat Diet	High n-6 Polyunsaturated Fat Diet
Arm/Group Description	SFA diet: Volunteers followed a high saturated fat diet for a 4-month period	MUFA diet: Volunteers followed a high monounsaturated fat diet for a 4-month period	n-6 PUFA diet: Volunteers followed a high n-6 polyunsaturated fat diet for a 4-month period
Period Title: Overall Study
STARTED	67	66	69
COMPLETED	65	64	66
NOT COMPLETED	2	2	3

Baseline Characteristics

Arm/Group Title	High Saturated Fat Diet	High Monounsaturated Fat Diet	High n-6 Polyunsaturated Fat Diet	Total
Arm/Group Description	SFA diet: Volunteers followed a high saturated fat diet for a 4-month period	MUFA diet: Volunteers followed a high monounsaturated fat diet for a 4-month period	n-6 PUFA diet: Volunteers followed a high n-6 polyunsaturated fat diet for a 4-month period	Total of all reporting groups
Overall Participants	65	64	66	195
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45 (9)	43 (11)	45 (10)	44 (10)
Sex: Female, Male (Count of Participants)
Female	36 55.4%	37 57.8%	37 56.1%	110 56.4%
Male	29 44.6%	27 42.2%	29 43.9%	85 43.6%
Region of Enrollment (participants) [Number]
United Kingdom	65 100%	64 100%	66 100%	195 100%
Body Mass Index (BMI) (kg/m^2) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [kg/m^2]	26.7 (4.4)	26.3 (3.9)	27.0 (3.7)	26.7 (4.0)
Waist Circumference (cm) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [cm]	92.1 (12.1)	88.2 (10.3)	92.1 (13.1)	90.9 (12.0)
24-hour Systolic Blood Pressure (SBP) (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	121 (12)	121 (10)	124 (11)	122 (11)
24-hour Diastolic Blood Pressure (DBP) (mm Hg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mm Hg]	75 (8)	74 (6)	76 (8)	75 (7)
Fasting Total Cholesterol (TC) (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	5.38 (0.98)	5.43 (1.07)	5.57 (1.27)	5.46 (1.09)
Fasting High-Density Lipoprotein Cholesterol (HDL-C) (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	1.45 (0.33)	1.48 (0.39)	1.51 (0.38)	1.48 (0.37)
Ratio of TC:HDL-C () [Mean (Standard Deviation) ]
Mean (Standard Deviation)	3.92 (1.20)	3.85 (0.99)	3.85 (1.12)	3.87 (1.10)
Fasting Low-Density Lipoprotein Cholesterol (LDL-C) (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	3.67 (0.93)	3.71 (0.88)	3.81 (1.13)	3.73 (0.98)
Fasting Triacylglycerol (TAG) (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	1.31 (0.77)	1.18 (0.53)	1.26 (0.67)	1.25 (0.67)
Fasting Glucose (mmol/L) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmol/L]	5.09 (0.43)	5.00 (0.45)	5.05 (0.44)	5.05 (0.44)

Outcome Measures

1. Primary Outcome

Title	Percent Change in Flow Mediated Dilatation (FMD)
Time Frame	Baseline, 4 months

Outcome Measure Data

Analysis Population Description

Number of participants analyzed: n=171. n=24 were images of poor quality that could not be analyzed successfully.

Arm/Group Title	High Saturated Fat Diet	High Monounsaturated Fat Diet	High n-6 Polyunsaturated Fat Diet
Arm/Group Description	SFA diet: Volunteers followed a high saturated fat diet for a 4-month period	MUFA diet: Volunteers followed a high monounsaturated fat diet for a 4-month period	n-6 PUFA diet: Volunteers followed a high n-6 polyunsaturated fat diet for a 4-month period
Measure Participants	59	57	55
Mean (Standard Error) [post-occlusion diameter change as %]	-0.39 (0.24)	-0.07 (0.32)	-0.08 (0.31)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	High Saturated Fat Diet, High Monounsaturated Fat Diet, High n-6 Polyunsaturated Fat Diet
	Comments	To detect a 2% inter-group difference in FMD (primary outcome) using a SD of 2.3, 90% power and 5% significance level, n=171 participants were required (n=57 per group), increasing to n=228 to include a 25% dropout rate.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.238
	Comments	Overall diet effect. No post-hoc analyses required. Adjusted for multiple comparisons.
	Method	General Linear Model Univariate Analysis
	Comments	Baseline values for %FMD, BMI, age, gender and intervention diet used as prognostic factors in model.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	High Saturated Fat Diet
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.021
	Comments	Effect of the SFA-rich diet relative to baseline.
	Method	General Linear Model Univariate Analysis
	Comments	Baseline values for %FMD, BMI and age, gender and intervention diet were used as prognostic factors in the model.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	High Monounsaturated Fat Diet
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments	Effect of MUFA-rich diet relative to baseline.
	Method	General Linear Model Univariate Analysis
	Comments	Baseline values for %FMD, BMI and age, gender and intervention diet were used as prognostic factors in the model.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	High n-6 Polyunsaturated Fat Diet
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	>0.05
	Comments	Effect of n-6 PUFA-rich diet relative to baseline.
	Method	General Linear Model Univariate Analysis
	Comments	Baseline values for %FMD, BMI and age, gender and intervention diet were used as prognostic factors in the model.

2. Secondary Outcome

Title	Cardiovascular Risk Factors (Lipids, Inflammatory Markers, Indices of Insulin Resistance, Cell Microparticles, Endothelial Progenitor Cells)
Description	Data for fasting serum lipids (total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), TC:HDL-C ratio, low-density lipoprotein cholesterol (LDL-C), triacylglycerol (TAG)).
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

3. Secondary Outcome

Title	24-hour Ambulatory Blood Pressure
Description	24-hour, daytime and night-time measures of systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP; SBP-DBP) and heart rate (HR)
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

4. Secondary Outcome

Title	Vascular Stiffness by Pulse Wave Velocity (PWV), Pulse Wave Analysis (PWA) and Digital Volume Pulse (DVP)
Description	PWV (m/s) PWA produces Augmentation Index (AIx; %) DVP produces Stiffness Index (SI; m/s) and Reflection Index (RI; %)
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Secondary Outcome

Title	Microvascular Reactivity (Laser Doppler Imaging With Iontophoresis)
Description	Laser Doppler imaging (LDI) with iontophoresis of acetylcholine (Ach; endothelium-dependent vasodilation) and sodium nitroprusside (SNP; endothelium-independent vasodilation).
Time Frame	4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Arm/Group Title	High Saturated Fat Diet		High Monounsaturated Fat Diet		High n-6 Polyunsaturated Fat Diet
Arm/Group Description	SFA diet: Volunteers followed a high saturated fat diet for a 4-month period		MUFA diet: Volunteers followed a high monounsaturated fat diet for a 4-month period		n-6 PUFA diet: Volunteers followed a high n-6 polyunsaturated fat diet for a 4-month period
All Cause Mortality
	High Saturated Fat Diet		High Monounsaturated Fat Diet		High n-6 Polyunsaturated Fat Diet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	High Saturated Fat Diet		High Monounsaturated Fat Diet		High n-6 Polyunsaturated Fat Diet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/67 (0%)		0/66 (0%)		0/69 (0%)
Other (Not Including Serious) Adverse Events
	High Saturated Fat Diet		High Monounsaturated Fat Diet		High n-6 Polyunsaturated Fat Diet
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/67 (0%)		0/66 (0%)		0/69 (0%)

Limitations/Caveats

[Not Specified]

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.