DyslipidaemiaPhase 2NCT01451918
Regulation of Intestinal and Hepatic Lipoprotein Secretion by Resveratrol
A Phase 2 study testing Resveratrol in people with Dyslipidaemia and Insulin Resistance, run by University Health Network, Toronto at 1 site in Canada.
Trial summary
Resveratrol, an ingredient of red wine and available in Canada in highly purified form as an over-the-counter health supplement, has been shown to have a number of health benefits. Data from in vitro and animal studies suggest that it has beneficial effects on insulin sensitivity and lipid lowering. Read more about this study
- Who is it for?
- Ages 23 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Dyslipidaemia, Insulin Resistance
- What is being tested?
- Resveratrol
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8 participants
- Where
- 1 siteCanada
- Study dates
- Oct 2011to Sep 2013
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 23 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Men and women, aged 23 to 60 years
- Fasting plasma triglycerides between 2.0 and 5.0 mmol/l
- Body mass index 25 kg/m2 to 35 kg/m2
- Minimum body weight 64kg
- Hemoglobin above 130g/L.
- Research volunteers must be able to provide informed consent and be willing to comply with protocol requirements.
- HOMA-IR (a measure of insulin resistance calculated from fasting blood glucose and insulin) >4.0.
- .
Who cannot join
- Subject has a history of hepatitis/hepatic disease that has been active within the previous two years.
- Any significant active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, renal (Cr > 1.5 mg/dL), genitourinary, hematological systems, or has severe uncontrolled treated or untreated hypertension (sitting diastolic BP > 90 or systolic >140) or proliferative retinopathy
- Any dehydration or excessive vomiting
- History of diabetes or 75g OGTT indicative of diabetes.
- Cancer or history of cancer
- Any history of a MI or clinically significant, active, cardiovascular history including a history of arrhythmia's or conduction delays on ECG, unstable angina, or decompensated heart failure.
Show all 23Show fewer
- Any active medical illness
- Any laboratory values: AST > 2x ULN; ALT > 2x ULN TSH>5mU/l or <0.01 mU/l
- Any clinically relevant abnormal blood/urine screening test results that are outside of the normal reference range and are significant to the investigator will be excluded
- Any current hormonal disorder or history or hormonal disorders
- Any bleeding disorders or autoimmune conditions
- Any allergies to any of the ingredients in the study product or placebo ie: hypersensitivity to resveratrol, grapes, red wine, red wine polyphenols and microcrystalline microcellulose
- Current addiction to alcohol or substances of abuse as determined by the investigator.
- Mental incapacity, unwillingness or language barrier precluding adequate understanding or cooperation
- Taking any prescription or non-prescription medications at the time of the study
- Taking any natural health products during the course of the study
- Having donated blood three months prior to and three months post study procedures
- A pregnancy test will be performed 1 to 3 days prior to each study in all female subjects (visit #4, and visit #7 before taking study drug). Those who test positive for pregnancy will be excluded.
- If you are breast-feeding or lactating you will be excluded from the study.
- Women taking the oral contraceptive pill will be excluded from the study.
- All current smokers or those who have smoked more than 1 pack per day for 5 years or more.
- Those with ferritin levels below 50 ug/L will be excluded
- Study Participants who experience serious adverse event or who no longer satisfy the inclusion /exclusion criteria during the trial will be withdrawn
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Regulation of Intestinal (and Hepatic) Lipoprotein Secretion by Resveratrol
Resveratrol, an ingredient of red wine and available in Canada in highly purified form as an over-the-counter health supplement, has been shown to have a number of health benefits. Data from in vitro and animal studies suggest that it has beneficial effects on insulin sensitivity and lipid lowering. The investigators are not aware, however, of any mechanistic studies that have examined the effect of highly purified resveratrol in vivo on lipoprotein metabolism in humans. Given the potential therapeutic benefit of resveratrol in correcting the metabolic abnormalities of insulin resistant individuals the investigators plan to examine the effects of resveratrol on intestinal and hepatic lipoprotein production in humans.
Read the detailed description
Subjects will receive resveratrol (Transmax 1 x 500mg tablets bid for one week followed by 2 x 500mg bid for the second week (Biotivia Longevity Biologicals, New York, NY, USA) or placebo and advised to start taking the tablets 14 days prior to the first lipoprotein kinetics study.
For the lipoprotein kinetics study subjects will receive an infusion of stable isotope enriched leucine and a bolus of stable isotope enriched glycerol in order to measure the rates of fatty acid synthesis, apolipoprotein and triglyceride turnover respectively. This in vivo stable isotope enrichment methodology has been widely established and used by investigators around the world for more than 30 years to examine the metabolism of various metabolites in humans.
On the first day of the 2 day admission to hospital for the lipoprotein kinetics study, following an overnight fast, at approximately noon on day 1 of the study the subject will be admitted to hospital and will have a 30ml fasting blood sample drawn for analysis of plasma glucose, total plasma cholesterol, LDL-cholesterol, HDL cholesterol, triglycerides (TG), free fatty acids (FFA), insulin, cytokines, stable isotope enrichment and a more detailed analysis of triglyceride rich lipoprotein (TRL) composition (lipid and apolipoprotein content). The subject will be allowed to eat regular meals during the day but will fast overnight after 7pm.
At 4am the subject will begin to ingest the first of 17 identical small hourly aliquots of a liquid formula called Great Shake Plus (Hormel), each hourly dose equivalent to 1/17th of their estimated daily caloric requirement calculated by the Harris-Benedict formula. Apart from the shake the subject will not eat until the end of the study at 7pm that night. This will provide a steady state fed state for the subsequent assessment of lipoprotein turnover kinetics. At 7am 2 iv's will be inserted into a superficial vein in each forearm, one for infusion and one for sampling.
At 7 am (the investigators will refer to this time point as 0hr of the lipoprotein turnover study), the lipoprotein turnover study will begin. An iv bolus of deuterated-glycerol (d5-glycerol, 75 micromol/kg) will be administered, followed by a primed-constant infusion of deuterated leucine (L-[5,5,5-2H3]-leucine; d3-leucine, 98%, Cambridge Isotope Laboratories, Andover, MA, USA)(10 micromol/kg bolus followed by 10 micromol/kg/hr for 10 hours). Blood samples will be collected prior to and at regular time intervals for 10 hours after the iv bolus of d3-glycerol (for 13C-triglyceride palmitate enrichment to assess de novo lipogenesis) and start of the constant infusion of d3-leucine (for assessment of lipoprotein kinetics). Insulin sensitivity will be assessed by calculation of HOMA-IR.
- Conditions
- Dyslipidaemia, Insulin Resistance
- Being tested
- Resveratrol
- Keywords
- Dyslipidaemia, Insulin resistance, Type 2 Diabetes
- Medical subject headings
- Dyslipidemias, Insulin Resistance, Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ResveratrolDrug
500mg bid for one week followed by 1 gram bid for one week prior to lipoprotein study.
| Study group | Role | What they receive |
|---|---|---|
| Resveratrol | Active comparator | Not described Receives: Drug: Resveratrol |
| Placebo | Placebo comparator | Not described Receives: Drug: Resveratrol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Examine the effect of resveratrol on ApoB 100 and ApoB 48 production in humans
10 hour lipoprotein turnover study as described above following 2 weeks treatment with resveratrol or placebo.
Measured: 2 weeks
Secondary outcomes (1)
Assess the change in insulin sensitivity with resveratrol treatment
HOMA-IR calculated from fasting insulin and fasting glucose will be used to assess change in insulin sensitivity before and after 2 weeks of resveratrol treatment.
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Oct 2011 (estimated)
- Study startOct 2011
- Primary completionSep 2013
- Study completionSep 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for DyslipidaemiaStudies of the same condition, open and under way.
- More trials run by University Health Network, TorontoThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Health Network, Toronto
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Responsible party
- Sponsor
- Investigators
- Gary Lewis, MD, Principal investigator, UHN Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01451918
- Sponsor's protocol ID
- RESV10-0537-A
- Status last verified
- May 2012
- First submitted
- 11 Oct 2011
- Last updated
- 6 May 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Dash S, Xiao C, Morgantini C, Szeto L, Lewis GF. High-dose resveratrol treatment for 2 weeks inhibits intestinal and hepatic lipoprotein production in overweight/obese men. Arterioscler Thromb Vasc Biol. 2013 Dec;33(12):2895-901. doi: 10.1161/ATVBAHA.113.302342. Epub 2013 Sep 26.
PubMed 24072699
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Regulation of Intestinal (and Hepatic) Lipoprotein Secretion by Resveratrol
- ClinicalTrials.gov ID
- NCT01451918
- Acronym / sponsor ID
- RESV10-0537-A
- Conditions
- Dyslipidaemia, Insulin Resistance
- Keywords
- Dyslipidaemia, Insulin resistance, Type 2 Diabetes
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- University Health Network, TorontoUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR)
- Study start
- Oct 2011
- Primary completion
- Sep 2013 (actual)
- Study completion
- Sep 2013 (actual)
- First posted
- 14 Oct 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Resveratrol, an ingredient of red wine and available in Canada in highly purified form as an over-the-counter health supplement, has been shown to have a number of health benefits. Data from in vitro and animal studies suggest that it has beneficial effects on insulin sensitivity and lipid lowering. The investigators are not aware, however, of any mechanistic studies that have examined the effect of highly purified resveratrol in vivo on lipoprotein metabolism in humans. Given the potential therapeutic benefit of resveratrol in correcting the metabolic abnormalities of insulin resistant individuals the investigators plan to examine the effects of resveratrol on intestinal and hepatic lipoprotein production in humans.
Detailed description
Subjects will receive resveratrol (Transmax 1 x 500mg tablets bid for one week followed by 2 x 500mg bid for the second week (Biotivia Longevity Biologicals, New York, NY, USA) or placebo and advised to start taking the tablets 14 days prior to the first lipoprotein kinetics study.
For the lipoprotein kinetics study subjects will receive an infusion of stable isotope enriched leucine and a bolus of stable isotope enriched glycerol in order to measure the rates of fatty acid synthesis, apolipoprotein and triglyceride turnover respectively. This in vivo stable isotope enrichment methodology has been widely established and used by investigators around the world for more than 30 years to examine the metabolism of various metabolites in humans.
On the first day of the 2 day admission to hospital for the lipoprotein kinetics study, following an overnight fast, at approximately noon on day 1 of the study the subject will be admitted to hospital and will have a 30ml fasting blood sample drawn for analysis of plasma glucose, total plasma cholesterol, LDL-cholesterol, HDL cholesterol, triglycerides (TG), free fatty acids (FFA), insulin, cytokines, stable isotope enrichment and a more detailed analysis of triglyceride rich lipoprotein (TRL) composition (lipid and apolipoprotein content). The subject will be allowed to eat regular meals during the day but will fast overnight after 7pm.
At 4am the subject will begin to ingest the first of 17 identical small hourly aliquots of a liquid formula called Great Shake Plus (Hormel), each hourly dose equivalent to 1/17th of their estimated daily caloric requirement calculated by the Harris-Benedict formula. Apart from the shake the subject will not eat until the end of the study at 7pm that night. This will provide a steady state fed state for the subsequent assessment of lipoprotein turnover kinetics. At 7am 2 iv's will be inserted into a superficial vein in each forearm, one for infusion and one for sampling.
At 7 am (the investigators will refer to this time point as 0hr of the lipoprotein turnover study), the lipoprotein turnover study will begin. An iv bolus of deuterated-glycerol (d5-glycerol, 75 micromol/kg) will be administered, followed by a primed-constant infusion of deuterated leucine (L-[5,5,5-2H3]-leucine; d3-leucine, 98%, Cambridge Isotope Laboratories, Andover, MA, USA)(10 micromol/kg bolus followed by 10 micromol/kg/hr for 10 hours). Blood samples will be collected prior to and at regular time intervals for 10 hours after the iv bolus of d3-glycerol (for 13C-triglyceride palmitate enrichment to assess de novo lipogenesis) and start of the constant infusion of d3-leucine (for assessment of lipoprotein kinetics). Insulin sensitivity will be assessed by calculation of HOMA-IR.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Resveratrol | Active comparator | Drug: Resveratrol |
| Placebo | Placebo comparator | Drug: Resveratrol |
Who may qualify
- Ages
- 23 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (8 listed)
- Men and women, aged 23 to 60 years
- Fasting plasma triglycerides between 2.0 and 5.0 mmol/l
- Body mass index 25 kg/m2 to 35 kg/m2
- Minimum body weight 64kg
- Hemoglobin above 130g/L.
Key exclusion criteria (23 listed)
- Subject has a history of hepatitis/hepatic disease that has been active within the previous two years.
- Any significant active (over the past 12 months) disease of the gastrointestinal, pulmonary, neurological, renal (Cr > 1.5 mg/dL), genitourinary, hematological systems, or has severe uncontrolled treated or untreated hypertension (sitting diastolic BP > 90 or systolic >140) or proliferative retinopathy
- Any dehydration or excessive vomiting
- History of diabetes or 75g OGTT indicative of diabetes.
- Cancer or history of cancer
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Resveratrol500mg bid for one week followed by 1 gram bid for one week prior to lipoprotein study. | Drug | Placebo, Resveratrol |
Primary outcome
Examine the effect of resveratrol on ApoB 100 and ApoB 48 production in humans
Time frame: 2 weeks
10 hour lipoprotein turnover study as described above following 2 weeks treatment with resveratrol or placebo.
1 secondary outcome
Assess the change in insulin sensitivity with resveratrol treatment
Time frame: 2 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2014.
- Derived from this study: PubMed 24072699Dash S, Xiao C, Morgantini C, Szeto L, Lewis GF. High-dose resveratrol treatment for 2 weeks inhibits intestinal and hepatic lipoprotein production in overweight/obese men. Arterioscler Thromb Vasc Biol. 2013 Dec;33(12):2895-901. doi: 10.1161/ATVBAHA.113.302342. Epub 2013 Sep 26.
Related trials for Dyslipidaemia
Active, not recruitingObservational study
Study Evaluating LDL-C Change and Adherence to Inclisiran Lipid-lowering Therapy in ASCVD
Primary Hypercholesterolemia, Mixed Dyslipidemia
Not yet recruiting
Plasma Lipids-Dependent Vitamin E Metabolism During Dynamic Hyperlipidemia
Lipid Metabolism Disorders
Active, not recruitingObservational study
A Longitudinal Cohort Study to Evaluate Cardiovascular Risk Factors and Disease in Haiti
Hypertension, Diabetes
Active, not recruiting
Developing a Learning COmmunity to Increase eNgagemeNt and Enrollment in Cardiovascular Clinical Trials (CONNECT)
Cardiovascular Diseases, Hypertension
Active, not recruitingPhase 3
A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary Prevention Patients.
Primary Prevention of Atherosclerotic Cardiovascular Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gary Lewis, MD principal investigator
UHN Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Resveratrol in people with Dyslipidaemia and Insulin Resistance, run by University Health Network, Toronto at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 23 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Examine the effect of resveratrol on ApoB 100 and ApoB 48 production in humans (time frame: 2 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01451918, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2014.