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

Tracking Information

• First Submitted Date: March 18, 2014
• First Posted Date: March 26, 2014
• Results First Submitted Date: August 2, 2016
• Results First Posted Date: March 6, 2017
• Last Update Posted Date: March 6, 2017
• Study Start Date: May 2014
• Actual Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 15, 2017)

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.

Original Primary Outcome Measures (submitted: March 24, 2014)

Change in oral glucose tolerance test (oGGT) [ Time Frame: Weeks 0, 10, 16 and 26 ]

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.

Current Secondary Outcome Measures (submitted: January 15, 2017)

• 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.
• 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.

Original Secondary Outcome Measures (submitted: March 24, 2014)

Change in finger-fold capillary density by capillaroscopy [ Time Frame: 0, 10, 16 and 26 weeks ]

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.

Current Other Pre-specified Outcome Measures (submitted: January 15, 2017)

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.

Original Other Pre-specified Outcome Measures (submitted: March 24, 2014)

• Change in aortal pulse wave velocity (aPWV) [ Time Frame: 0, 10, 16 and 26 weeks ]
  Aortal pulse wave velocity is measured by a non-invasive oscillometric device.
• Change in flow-mediated dilatation (FMD) [ Time Frame: 0, 10, 16 and 26 weeks ]
  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.

Descriptive Information

• Brief Title: Healthy Aging Through Functional Food
• Official Title: Dietary Inducers of Glyoxalase-1 for Prevention and Early-stage Alleviation of Age Related Health Disorders Through Functional Foods.
• Brief Summary: The purpose of this study is to determine whether dietary inducers of glyoxalase 1 are effective in improving metabolic and vascular health.

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 Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment

Condition

• Glucose Intolerance
• Aortic Stiffness
• Vasodilation

Intervention

• Dietary Supplement: Glyoxalase 1 (Glo1) inducer
  Dietary bioactive
  Other Name: trans-resveratrol, 90 mg + hesperetin, 120 mg (combination)
• Dietary Supplement: Placebo
  Mannitol, 108 mg

Study Arms

• Experimental: Glo1-inducer then placebo
  Glyoxalase 1 Inducer (8 weeks), then washout (6 weeks), then Placebo (8 weeks).
  Interventions:

  • Dietary Supplement: Glyoxalase 1 (Glo1) inducer
  • Dietary Supplement: Placebo
• Experimental: Placebo then Glo1-inducer
  Placebo (8 weeks), then washout (6 weeks), then Glyoxalase 1 Inducer (8 weeks).
  Interventions:

  • Dietary Supplement: Glyoxalase 1 (Glo1) inducer
  • Dietary Supplement: Placebo

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.
• 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 24, 2014): 32
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: May 2015
• Actual Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 80 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United Kingdom

Administrative Information

• NCT Number: NCT02095873
• Other Study ID Numbers: PJT_HATFF; TSB101129 ( Other Identifier: University of Warwick )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes

• Current Responsible Party: Professor Paul J. Thornalley, University of Warwick
• Original Responsible Party: Same as current
• Current Study Sponsor: University of Warwick
• Original Study Sponsor: Same as current

Collaborators

• 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

• PRS Account: University of Warwick
• Verification Date: January 2017