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| ID | Type | Description | Link |
|---|---|---|---|
| TSB101129 | Other Identifier | University of Warwick |
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| Name | Class |
|---|---|
| Technology Strategy Board, United Kingdom | OTHER |
| Unilever R&D | INDUSTRY |
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The purpose of this study is to determine whether dietary inducers of glyoxalase 1 are effective in improving metabolic and vascular health.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Glo1-inducer then placebo | Experimental | Glyoxalase 1 Inducer (8 weeks), then washout (6 weeks), then Placebo (8 weeks). |
|
| Placebo then Glo1-inducer | Experimental | Placebo (8 weeks), then washout (6 weeks), then Glyoxalase 1 Inducer (8 weeks). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Glyoxalase 1 (Glo1) inducer | Dietary Supplement | Dietary bioactive |
|
| Measure | Description | Time Frame |
|---|---|---|
| Area Under the Curve for Oral Glucose Tolerance Test (oGGT) | 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. | Week 0 and Week 8 (first intervention); Week 14 and Week 22 (second intervention) |
| Measure | Description | Time Frame |
|---|---|---|
| Finger-fold Capillary Density by Capillaroscopy | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Aortal Pulse Wave Velocity (aPWV) | Aortal pulse wave velocity is measured by a non-invasive oscillometric device. | Week 0 and Week 8 (first intervention); Week 14 and Week 22 (second intervention) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Paul J Thornalley, BSc PhD | University of Warwick | Study Chair |
| Martin O Weickert, MD | University Hospitals Coventry & Warwickshire NHS Trust | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospitals Coventry & Warwickshire NHS Trust (UHCW) | Coventry | Warwickshire | CV22DX | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22188542 | Background | 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. | |
| 25666945 | Background |
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| ID | Title | Description |
|---|---|---|
| FG000 | Glyoxalase 1 Inducer First, Then Placebo | 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. |
| FG001 | Placebo Then Glyoxalase 1 Inducer | 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. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| First Intervention (8 Weeks) |
|
| ||||||||||||||||||
| Second Intervention (8 Weeks) |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Glyoxalase 1 Inducer Then Placebo | Glyoxalase 1 inducer (90 mg trans-resveratrol & 120 mg hesperetin), once daily, 8 weeks; then Placebo (excipient: 108 mg mannitol), once daily, 8 weeks. |
| BG001 | Placebo Then Glyoxalase 1 Inducer |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Area Under the Curve for Oral Glucose Tolerance Test (oGGT) | 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. | Highly overweight/obese (BMI>27.5 kg/m2) subgroup, based on subject BMI at study entry. | Posted | Mean | Standard Error | mM h | Week 0 and Week 8 (first intervention); Week 14 and Week 22 (second intervention) |
|
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.
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Glo1-inducer Then Placebo | 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. |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Paul J Thornalley | University of Warwick | +442476968594 | P.J.Thornalley@warwick.ac.uk |
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| ID | Term |
|---|---|
| D018149 | Glucose Intolerance |
| D000783 | Aneurysm |
| ID | Term |
|---|---|
| D006943 | Hyperglycemia |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D007791 | Lactoylglutathione Lyase |
| D000077185 | Resveratrol |
| C013015 | hesperetin |
| ID | Term |
|---|---|
| D013437 | Carbon-Sulfur Lyases |
| D008190 | Lyases |
| D004798 | Enzymes |
| D045762 | Enzymes and Coenzymes |
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| Placebo | Dietary Supplement | Mannitol, 108 mg |
|
| Week 0 and Week 8 (first intervention); Week 14 and Week 22 (second intervention) |
| Flow-mediated Dilatation (FMD) | 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. | Week 0 and Week 8 (first intervention); Week 14 and Week 22 (second intervention) |
| 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. |
| 27207552 | Result | 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. |
| NOT COMPLETED |
|
|
Placebo (excipient: 108 mg mannitol), once daily, 8 weeks; then Glyoxalase 1 inducer (90 mg trans-resveratrol & 120 mg hesperetin), once daily, 8 weeks.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Gender | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
Glyoxalase 1 inducer (90 mg trans-resveratrol & 120 mg hesperetin), once daily, 8 weeks. |
| OG001 | Placebo | Placebo (excipient: 108 mg mannitol), capsule, once daily, 8 weeks. |
|
|
| Secondary | Finger-fold Capillary Density by Capillaroscopy | 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. | All subjects with where baseline and post-8 treatment data were obtained. | Posted | Median | Inter-Quartile Range | number of capillaries per mm2 | Week 0 and Week 8 (first intervention); Week 14 and Week 22 (second intervention) |
|
|
|
| Secondary | Flow-mediated Dilatation (FMD) | 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. | All subjects completing the study per protocol | Posted | Median | Inter-Quartile Range | percentage of baseline value | Week 0 and Week 8 (first intervention); Week 14 and Week 22 (second intervention) |
|
|
|
| Other Pre-specified | Aortal Pulse Wave Velocity (aPWV) | Aortal pulse wave velocity is measured by a non-invasive oscillometric device. | Subjects for which PWV data were obtained at baseline and post 8-weeks treatment. | Posted | Median | Inter-Quartile Range | m/s | Week 0 and Week 8 (first intervention); Week 14 and Week 22 (second intervention) |
|
|
|
| 0 |
| 16 |
| 0 |
| 16 |
| EG001 | Placebo Then Glo1-inducer | 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. | 0 | 16 | 0 | 16 |
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| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D000081225 |
| Stilbestrols |
| D013267 | Stilbenes |
| D001597 | Benzylidene Compounds |
| D001555 | Benzene Derivatives |
| D006841 | Hydrocarbons, Aromatic |
| D006844 | Hydrocarbons, Cyclic |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D059808 | Polyphenols |
| D010636 | Phenols |