HATFF: Healthy Aging Through Functional Food

• Sponsor: University of Warwick (Other)
• Overall Status: Completed
• CT.gov ID: NCT02095873
• Collaborator: Technology Strategy Board, United Kingdom (Other), Unilever R&D (Industry)
• Enrollment: 32
• Location: 1
• Arms: 2
• Duration (Months): 12
• Patients Per Site Per Month: 2.7

Study Details

Study Description

Brief Summary

The purpose of this study is to determine whether dietary inducers of glyoxalase 1 are effective in improving metabolic and vascular health.

Condition or Disease	Intervention/Treatment	Phase
Glucose Intolerance; Aortic Stiffness; Vasodilation	Dietary Supplement: Glyoxalase 1 (Glo1) inducer; Dietary Supplement: Placebo	Phase 1/Phase 2

Detailed Description

The aim of the study is to evaluate dietary inducers of glyoxalase 1 for effects on metabolic and vascular health in overweight volunteers at risk of developing type 2 diabetes. The research objectives are:

(i) To evaluate dietary inducers of glyoxalase 1 for effects on markers of glucose metabolism during an oral glucose tolerance test (oGTT), (ii) To evaluate dietary inducers of glyoxalase 1 for effects on vascular function on three levels, using finger fold capillary density by capillaroscopy (FFCD), arterial stiffness by aortal pulse wave velocity (aPWV) and flow mediated dilatation (FMD); and effects on metabolic and pro-inflammatory markers in circulating blood and urine.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Dietary Inducers of Glyoxalase-1 for Prevention and Early-stage Alleviation of Age Related Health Disorders Through Functional Foods.
• Study Start Date: May 1, 2014
• Actual Primary Completion Date: Feb 1, 2015
• Actual Study Completion Date: May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Glo1-inducer then placebo Glyoxalase 1 Inducer (8 weeks), then washout (6 weeks), then Placebo (8 weeks).	Dietary Supplement: Glyoxalase 1 (Glo1) inducer; Dietary bioactive; Other Names: trans-resveratrol, 90 mg + hesperetin, 120 mg (combination) ; Dietary Supplement: Placebo; Mannitol, 108 mg
Experimental: Placebo then Glo1-inducer Placebo (8 weeks), then washout (6 weeks), then Glyoxalase 1 Inducer (8 weeks).	Dietary Supplement: Glyoxalase 1 (Glo1) inducer; Dietary bioactive; Other Names: trans-resveratrol, 90 mg + hesperetin, 120 mg (combination) ; Dietary Supplement: Placebo; Mannitol, 108 mg

Outcome Measures

Primary Outcome Measures

1. Area Under the Curve for Oral Glucose Tolerance Test (oGGT) [Week 0 and Week 8 (first intervention); Week 14 and Week 22 (second intervention)]

   A standard 75 g glucose oGTT will be performed, as routinely used in clinical practice. Participants will be instructed to eat carbohydrate rich diet (> 150 g/day) for at least three days before the test, followed by an overnight fast. Participants will be instructed to have comparable macronutrient composition of the dinner before the respective study days in the metabolic unit. During the oGTT both capillary and venous blood samples will be collected after 0, 15, 30, 60, 90 and 120 min. To minimize the inconvenience of repeated blood tests during the oGTT, a venous cannula will be inserted, under sterile conditions, prior to the test, for blood sampling.

Secondary Outcome Measures

1. Finger-fold Capillary Density by Capillaroscopy [Week 0 and Week 8 (first intervention); Week 14 and Week 22 (second intervention)]

   After 20 min seated at rest, measurements are made with the subject seated and the left hand at heart level. Nail-fold capillaries in the dorsal skin of the third finger are visualized using a stereo microscope linked to a monochrome digital camera. Capillary density is defined as the number of capillaries per mm2 of nail-fold skin and is computed as the mean of 4 measurements.

2. Flow-mediated Dilatation (FMD) [Week 0 and Week 8 (first intervention); Week 14 and Week 22 (second intervention)]

   Brachial artery FMD will be assessed. Ultrasound imaging of the brachial artery will be performed. Percent FMD will be calculated using the averaged minimum mean brachial artery diameter at baseline compared to the largest mean values obtained after either release of the forearm occlusion.

Other Outcome Measures

1. Aortal Pulse Wave Velocity (aPWV) [Week 0 and Week 8 (first intervention); Week 14 and Week 22 (second intervention)]

   Aortal pulse wave velocity is measured by a non-invasive oscillometric device.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 80 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• BMI 25 - 40 kg/m2 (>23 kg/m2 for Asians), with normal, impaired fasting or impaired postprandial glucose.

• No other relevant morbidities.

• Women will be preferably post-menopausal.

Exclusion Criteria:

• Severe hypertriglyceridemia.

• Uncontrolled hypertension, cardiovascular disease, relevant renal or hepatic disease, diabetes, and other relevant morbidity.

• Excess alcohol consumption, smoking, acute pharmacological treatment with drugs affecting glucose metabolism such as steroids and antibiotics.

• Anticoagulants.

• Intake of herbal remedies.

• Food allergies.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospitals Coventry & Warwickshire NHS Trust (UHCW)	Coventry	Warwickshire	United Kingdom	CV22DX

Sponsors and Collaborators

• University of Warwick
• Technology Strategy Board, United Kingdom
• Unilever R&D

Investigators

• Study Chair: Paul J Thornalley, BSc PhD, University of Warwick
• Principal Investigator: Martin O Weickert, MD, University Hospitals Coventry & Warwickshire NHS Trust

Study Documents (Full-Text)

None provided.

More Information

Publications

• Rabbani N, Thornalley PJ. Dicarbonyl stress in cell and tissue dysfunction contributing to ageing and disease. Biochem Biophys Res Commun. 2015 Mar 6;458(2):221-6. doi: 10.1016/j.bbrc.2015.01.140. Epub 2015 Feb 7. Review.
• Xue M, Rabbani N, Momiji H, Imbasi P, Anwar MM, Kitteringham N, Park BK, Souma T, Moriguchi T, Yamamoto M, Thornalley PJ. Transcriptional control of glyoxalase 1 by Nrf2 provides a stress-responsive defence against dicarbonyl glycation. Biochem J. 2012 Apr 1;443(1):213-22. doi: 10.1042/BJ20111648.

• Responsible Party: Professor Paul J. Thornalley, Professor, University of Warwick
• ClinicalTrials.gov Identifier: NCT02095873
• Other Study ID Numbers: PJT_HATFF; TSB101129
• First Posted: Mar 26, 2014
• Last Update Posted: Mar 6, 2017
• Last Verified: Jan 1, 2017

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Professor Paul J. Thornalley, Professor, University of Warwick: Oral glucose tolerance test; Flow mediated dilatation; Aortal pulse wave velocity; Finger-fold capillary density by capillaroscopy
• Additional relevant MeSH terms: Glucose Intolerance; Resveratrol

Study Results

Participant Flow

Arm/Group Title	Glyoxalase 1 Inducer First, Then Placebo	Placebo Then Glyoxalase 1 Inducer
Arm/Group Description	Glyoxalase 1 inducer (capsule, 90 mg trans-resveratrol & 120 mg hesperetin combination) once daily, 8 weeks; then Placebo (excipient: Mannitol, 108 mg) once daily, 8 weeks.	Placebo (excipient: Mannitol, 108 mg), once daily, 8 weeks; then Glyoxalase 1 inducer (capsule, 90 mg trans-resveratrol & 120 mg hesperetin combination) once daily, 8 weeks.
Period Title: First Intervention (8 Weeks)
STARTED	16	16
COMPLETED	15	16
NOT COMPLETED	1	0
Period Title: First Intervention (8 Weeks)
STARTED	15	16
COMPLETED	13	16
NOT COMPLETED	2	0

Baseline Characteristics

Arm/Group Title	Glyoxalase 1 Inducer Then Placebo	Placebo Then Glyoxalase 1 Inducer	Total
Arm/Group Description	Glyoxalase 1 inducer (90 mg trans-resveratrol & 120 mg hesperetin), once daily, 8 weeks; then Placebo (excipient: 108 mg mannitol), once daily, 8 weeks.	Placebo (excipient: 108 mg mannitol), once daily, 8 weeks; then Glyoxalase 1 inducer (90 mg trans-resveratrol & 120 mg hesperetin), once daily, 8 weeks.	Total of all reporting groups
Overall Participants	15	17	32
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	45 (12)	44 (13)	45 (13)
Gender (Count of Participants)
Female	10 66.7%	12 70.6%	22 68.8%
Male	5 33.3%	5 29.4%	10 31.3%
Region of Enrollment (participants) [Number]
United Kingdom	15 100%	17 100%	32 100%

Outcome Measures

1. Primary Outcome

Title	Area Under the Curve for Oral Glucose Tolerance Test (oGGT)
Description	A standard 75 g glucose oGTT will be performed, as routinely used in clinical practice. Participants will be instructed to eat carbohydrate rich diet (> 150 g/day) for at least three days before the test, followed by an overnight fast. Participants will be instructed to have comparable macronutrient composition of the dinner before the respective study days in the metabolic unit. During the oGTT both capillary and venous blood samples will be collected after 0, 15, 30, 60, 90 and 120 min. To minimize the inconvenience of repeated blood tests during the oGTT, a venous cannula will be inserted, under sterile conditions, prior to the test, for blood sampling.
Time Frame	Week 0 and Week 8 (first intervention); Week 14 and Week 22 (second intervention)

Outcome Measure Data

Analysis Population Description

Highly overweight/obese (BMI>27.5 kg/m2) subgroup, based on subject BMI at study entry.

Arm/Group Title	Glyoxalase 1 Inducer	Placebo
Arm/Group Description	Glyoxalase 1 inducer (90 mg trans-resveratrol & 120 mg hesperetin), once daily, 8 weeks.	Placebo (excipient: 108 mg mannitol), capsule, once daily, 8 weeks.
Measure Participants	20	20
Baseline	10.8 (0.7)	11.0 (0.7)
Post-8 weeks treatment	9.9 (0.6)	10.6 (0.6)

2. Secondary Outcome

Title	Finger-fold Capillary Density by Capillaroscopy
Description	After 20 min seated at rest, measurements are made with the subject seated and the left hand at heart level. Nail-fold capillaries in the dorsal skin of the third finger are visualized using a stereo microscope linked to a monochrome digital camera. Capillary density is defined as the number of capillaries per mm2 of nail-fold skin and is computed as the mean of 4 measurements.
Time Frame	Week 0 and Week 8 (first intervention); Week 14 and Week 22 (second intervention)

Outcome Measure Data

Analysis Population Description

All subjects with where baseline and post-8 treatment data were obtained.

Arm/Group Title	Glyoxalase 1 Inducer	Placebo
Arm/Group Description	Glyoxalase 1 inducer (capsule, 90 mg trans-resveratrol & 120 mg hesperetin combination) once daily, 8 weeks.	Placebo (excipient: Mannitol, 108 mg), once daily, 8 weeks.
Measure Participants	28	24
Baseline	115	119
Post-8 weeks treatment	125	128

3. Secondary Outcome

Title	Flow-mediated Dilatation (FMD)
Description	Brachial artery FMD will be assessed. Ultrasound imaging of the brachial artery will be performed. Percent FMD will be calculated using the averaged minimum mean brachial artery diameter at baseline compared to the largest mean values obtained after either release of the forearm occlusion.
Time Frame	Week 0 and Week 8 (first intervention); Week 14 and Week 22 (second intervention)

Outcome Measure Data

Analysis Population Description

All subjects completing the study per protocol

Arm/Group Title	Glyoxalase 1 Inducer	Placebo
Arm/Group Description	Glyoxalase 1 inducer (capsule, 90 mg trans-resveratrol & 120 mg hesperetin combination) once daily, 8 weeks.	Placebo (excipient: Mannitol, 108 mg), once daily, 8 weeks.
Measure Participants	29	29
Baseline	0.17	0.18
Post-8 weeks treatment	0.12	0.26

4. Other Pre-specified Outcome

Title	Aortal Pulse Wave Velocity (aPWV)
Description	Aortal pulse wave velocity is measured by a non-invasive oscillometric device.
Time Frame	Week 0 and Week 8 (first intervention); Week 14 and Week 22 (second intervention)

Outcome Measure Data

Analysis Population Description

Subjects for which PWV data were obtained at baseline and post 8-weeks treatment.

Arm/Group Title	Glyoxalase 1 Inducer	Placebo
Arm/Group Description	Glyoxalase 1 inducer (capsule, 90 mg trans-resveratrol & 120 mg hesperetin combination) once daily, 8 weeks.	Placebo (excipient: Mannitol, 108 mg), once daily, 8 weeks.
Measure Participants	13	12
Baseline	7.9	8.3
Post-8 weeks treatment	8.0	8.5

Adverse Events

Time Frame	From baseline to study completion: 8 weeks Glo1-inducer, 6 weeks washout then 8 weeks placebo; or 8 weeks placebo, 6 weeks washout then 8 weeks Glo1-inducer.
Adverse Event Reporting Description	All potential clinical adverse effects were monitoring including nausea, loss of appetite, gastrointestinal side effects and other symptoms. Clinical chemistry and haematological assessments were also made.
Arm/Group Title	Glo1-inducer Then Placebo		Placebo Then Glo1-inducer
Arm/Group Description	Glyoxalase 1 inducer: capsule, 90 mg trans-resveratrol & 120 mg hesperetin, once daily for 8 weeks; then 6-weeks washout; then placebo capsule (mannitol, 210 mg), once daily for 8 weeks.		Placebo capsule (mannitol, 210 mg), once daily for 8 weeks; then 6-weeks washout; then Glyoxalase 1 inducer: capsule, 90 mg trans-resveratrol & 120 mg hesperetin, once daily for 8 weeks.
All Cause Mortality
	Glo1-inducer Then Placebo		Placebo Then Glo1-inducer
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Glo1-inducer Then Placebo		Placebo Then Glo1-inducer
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (0%)
Other (Not Including Serious) Adverse Events
	Glo1-inducer Then Placebo		Placebo Then Glo1-inducer
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/16 (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.