Healthy Aging Through Functional Food (HATFF)

• ClinicalTrials.gov Identifier: NCT02095873
• Recruitment Status: Completed
• First Posted: March 26, 2014
• Results First Posted: March 6, 2017
• Last Update Posted: March 6, 2017
• Sponsor: University of Warwick
• Collaborators: Technology Strategy Board, United Kingdom; Unilever R&D
• Information provided by (Responsible Party): Professor Paul J. Thornalley, University of Warwick

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 (Clinical Trial)
• 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 2014
• Actual Primary Completion Date: February 2015
• Actual Study Completion Date: May 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 Name: 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 Name: 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) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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) [ Time Frame: 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

• Ages Eligible for Study: 18 Years to 80 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

United Kingdom

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

More Information

Publications of Results:

Xue M, Weickert MO, Qureshi S, Kandala NB, Anwar A, Waldron M, Shafie A, Messenger D, Fowler M, Jenkins G, Rabbani N, Thornalley PJ. Improved Glycemic Control and Vascular Function in Overweight and Obese Subjects by Glyoxalase 1 Inducer Formulation. Diabetes. 2016 Aug;65(8):2282-94. doi: 10.2337/db16-0153. Epub 2016 May 11.

Other Publications:

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.

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.

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

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes

Keywords provided by Professor Paul J. Thornalley, 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; Hyperglycemia; Glucose Metabolism Disorders; Metabolic Diseases; Resveratrol; Antioxidants; Molecular Mechanisms of Pharmacological Action; Protective Agents; Physiological Effects of Drugs; Enzyme Inhibitors; Platelet Aggregation Inhibitors