Diabetes Mellitus, Type 2Phase 1NCT01031108
A Clinical Trial to Assess the Safety of Oral SRT2104 and Its Effects on Vascular Dysfunction in Otherwise Healthy Cigarette Smokers and Subjects With Type 2 Diabetes Mellitus
A Phase 1 study testing SRT2104 in people with Diabetes Mellitus, Type 2, run by Sirtris, a GSK Company at 1 site in United Kingdom.
Trial summary
The primary purpose of this study is to evaluate the safety and tolerability of SRT2104 (2.0 g administered once daily for 28 days) and to examine the effects of SRT2104 (2.0 g administered once daily for 28 days) on reversing vasomotor and fibrinolytic dysfunction in both type 2 diabetes mellitus patients and… Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- SRT2104
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 38 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 28 May 2010to 12 Oct 2011
- Phase
- Phase 1
- 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 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Ambulatory male and female subjects (of any race) either with type 2 diabetes or otherwise healthy cigarette smokers (≥ 10 cigarettes/day for at least 1 year) within the age range of 18-70 years (inclusive) at the time of Screening.
- If a subject is diabetic, HbA1c at Screening is < 9.0%
- If a subject is diabetic, fasting plasma glucose (FPG) ≤ 13.875 mmol/L (≤ 250 mg/dL).
- If a subject is diabetic, an official diagnosis of type 2 diabetes must be documented for at least 6 months prior to first dose of test article.
- If a subject is diabetic, subject must be on an existing, stable, hypoglycemic therapy or a stable dietary regimen to control their disease for at least 3 months prior to Screening.
- Note: If a subject is a diabetic and a smoker, then they are not eligible for the trial. A minimum 5 year non-smoking history is required for all type 2 diabetic subjects to be enrolled into the study.
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- Female subjects of child-bearing potential, willing to use reliable contraception (see Section 5.10) for the duration of the study, through to the 30 day safety follow up visit (a female of child-bearing potential is defined as any female, regardless of her age with functioning ovaries and no documented impairment of oviductal or uterine function that would cause sterility. Females with oligomenorrhea or who are perimenopausal, and young females who have begun to menstruate are considered to be of child-bearing potential)
- All male subjects must agree with their partners to use double-barrier birth control or abstinence while participating in the study and for 12 weeks following the last dose of study drug.
- Willingness to provide written informed consent to participate in the study.
- Subject may be on concomitant treatments for other conditions, provided the medical condition necessitating the treatment and therapy is stable for at least 3 months prior to screening and the treatment is not counterindicated by the study protocol.
- Subject is not currently on a therapeutic regimen of ACE inhibitors, anti-coagulants, anti-platelets, or any other medications or treatments which may influence coagulation (with the exception of 81 mg or less of aspirin/acetylsalicylic acid daily).
- Body Mass Index (BMI) of 18.5-38 kg/m^2 (inclusive).
- Resting supine blood pressure (BP) <160/90 mmHg.
- Absence of significant disease (other than type 2 diabetes) or clinically significant abnormal laboratory values on the laboratory evaluations, medical history, or physical examination during screening; normal end organ function at the discretion of the principal investigator.
- Negative test result at screening for HIV 1 and 2.
- Negative test result at screening for hepatitis B \& C virus.
- Have a normal 12-lead electrocardiogram (ECG) or one with changes considered to be clinically insignificant on medical review. QTcB must be < 450 msec for males and females. QTcB must be <480 msec in subjects with Bundle Branch Block.
- Comprehension of the nature and purpose of the study and compliance with the requirements of the entire protocol.
- Able to communicate in person and by telephone in a manner that allows all protocol procedures to be carried out safety and reliably in the opinion of the investigative site staff.
Who cannot join
- If diabetic, any major illness in the past 3 months or any significant ongoing chronic medical illness not related to diabetes which in the opinion of the principal investigator or medical monitor could risk subject safety or interpretation of the results.
- If an otherwise healthy cigarette smoker, any major illness or injury in the past 3 months or any significant ongoing chronic medical illness (including diabetes) which in the opinion of the principal investigator or medical monitor could risk subject safety or interpretation of the results.
- Renal or liver impairment, defined as alkaline phosphatase and/or bilirubin ≥ 1.5 x ULN (an isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin is <35%), serum creatinine level of ≥ 123.76 µmol/L (≥ 1.4 mg/dL ) in females and ≥ 132.60 µmol/L (≥ 1.5 mg/dL ) in males, and > 2 × ULN for liver transaminases (ALT and AST), respectively.
- History of or current gastrointestinal diseases or surgeries influencing drug absorption, except for appendectomy.
- History, within 3 years, of drug abuse (including benzodiazepines, opioids, amphetamine, cocaine, and THC).
- History of alcoholism (more than 2 years), moderate drinkers (more than three drinks per day) or having consumed alcohol within 48 hours prior to first dose of test article (one drink is equal to one unit of alcohol [one glass wine, half pint beer, one measure of spirit]).
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- Participation in any clinical trial within the past 3 months prior to the first dose of test article in the current study.
- History of difficulty in donating blood or accessibility of veins in left or right arm.
- Donation of blood or loss of blood (greater than 500 mL) within 3 months prior to receiving the first dose of test material.
- Use of any dietary or herbal supplements within 2 weeks prior the first dose of study drug, with the exception of an Investigator approved vitamin.
- History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the investigator or medical monitor, contraindicates their participation.
- Active neoplastic disease or history of neoplastic disease within 5 years of study entry (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ).
- A positive pre-study drug screen.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase I, Randomized, Placebo-Controlled, Crossover Clinical Trial to Assess the Safety of Oral SRT2104 and Its Effects on Vascular Dysfunction in Otherwise Healthy Cigarette Smokers and Subjects With Type 2 Diabetes Mellitus
The primary purpose of this study is to evaluate the safety and tolerability of SRT2104 (2.0 g administered once daily for 28 days) and to examine the effects of SRT2104 (2.0 g administered once daily for 28 days) on reversing vasomotor and fibrinolytic dysfunction in both type 2 diabetes mellitus patients and otherwise healthy cigarette smokers in a fed state.
This study will investigate the effects of SRT2104 on the reduction of platelet activation markers (platelet-monocyte aggregates), and to evaluate the effects of SRT2104 on platelet and monocyte surface markers (P-selectin, CD11b), inflammatory markers (high sensitivity CRP, IL-6, SAA, TNF-α and sCD40L), and markers of oxidative stress (urinary and plasma F2-isoprostanes and nitrotyrosine).
Further goals of this study is to characterize the pharmacokinetic profile of SRT2104 after a single dose and multiple administrations in both type 2 diabetes mellitus patients and otherwise healthy cigarette smokers in a fed state, and to explore the effects of SRT2104 on potential biomarkers of activity for glucose control (HbA1c, glycated albumin and fructosamine) and/or Sirt1 activation.
Read the detailed description
Single-center, randomized, double-blind, placebo-controlled, crossover, safety, activity, and pharmacokinetic (PK) study of 2.0 g of SRT2104 administered orally once daily for 28 consecutive days to two different populations: type 2 diabetic (T2D) subjects on an existing, stable, hypoglycemic regimen and otherwise healthy cigarette smokers (≥ 10cigarettes/day for at least 1 year). Approximately 24 subjects with T2D and 24 otherwise healthy cigarette smokers, aged 18-60 years, who fulfill the inclusion/exclusion criteria, will be enrolled in this study to ensure at least 20 evaluable subjects per population are enrolled. Subjects will be evenly stratified and randomized to receive SRT2104 2.0 g/day or placebo once daily for 28 days. After 28 days, subjects will cross over to receive the other test article for another 28 days of dosing, bringing the total dosing period to 56 days.
Subjects will sign the informed consent form at the screening visit (to occur within 21 days of first dose of test article), and will undergo screening assessments to verify eligibility for the study. If eligible and willing to participate, subjects will return to the clinic on Days -1 and 1 for safety assessments, hematology and biochemistry measurements, platelet monocyte aggregation (PMA) assessment, forearm venous occlusion plethysmography, pulse wave analysis (PWA), pulse wave velocity (PWV) and PK sampling. The first dose of test article will occur on Day 1 after eligibility has been confirmed. After each 28 day dosing period, subjects will return on Day 28 and Day 56 for safety assessments, hematology and biochemistry measurements, forearm plethysmography, PWA, PWV, and PK sampling. Subjects will return to the clinic on Days 2, 15, 29, 43, and 57 for safety assessments and additional PK sampling. Subjects will be asked to complete a study drug diary on a daily basis for compliance and adverse event (AE) monitoring (diabetic subjects will be required to monitor and record their fasting blood glucose in the diary also). An End of Study visit will occur 14 days following the final dose of SRT2104 or placebo on Day 70. A followup safety call will be made to each subject 30 days following their final dose of SRT2104 or placebo (Day 86).
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- Placebo, SRT2104
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
For the placebo product, SRT2104 drug substance will be replaced by microcrystalline cellulose (Avicel® PH 105) to match the SRT2104 investigational product.
Eight placebo capsules are stored in a dosing bottle and provided to all participating subjects for oral ingestion.
SRT2104Drug
SRT2104 investigational product is a size 00 Swedish Orange opaque hard gelatin capsule containing 0.25 g of SRT2104, a new chemical entity which is supplied as a micronized, yellowish/amber powder. Eight SRT2104 capsules are stored in a dosing bottle and provided to all participating subjects for oral ingestion.
| Study group | Role | What they receive |
|---|---|---|
| Type 2 Diabetic Group | Other | The Type 2 Diabetic Treatment Group will be randomized to receive test material (2.0g SRT2104 or placebo) in the form of 8 capsules per day for 28 days. After 28 days of dosing, subjects will cross over to receive placebo or 2.0g SRT2104 for an additional 28 days. Dosing of SRT2104 or placebo will take place at approximately the same time every morning, approximately 15 minutes following consumption of a standardized morning meal (220 cc of Ensure Plus®). Subjects must wait at least 1-2 hours after dosing before consuming additional calories. Water is permitted ad libitum. Receives: Drug: Placebo; Drug: SRT2104 |
| Otherwise Healthy Cigarette Smoking Group | Other | The Otherwise Healthy Cigarette Smoking Treatment Group will be randomized to receive test material (2.0g SRT2104 or placebo) in the form of 8 capsules per day for 28 days. After 28 days of dosing, subjects will cross over to receive placebo or 2.0g SRT2104 for an additional 28 days. Dosing of SRT2104 or placebo will take place at approximately the same time every morning, approximately 15 minutes following consumption of a standardized morning meal (220 cc of Ensure Plus®). Subjects must wait at least 1-2 hours after dosing before consuming additional calories. Water is permitted ad libitum. Receives: Drug: Placebo; Drug: SRT2104 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To evaluate the safety and tolerability of SRT2104 (2.0 g administered once daily for 28 days) in both type 2 diabetes mellitus patients and otherwise healthy cigarette smokers in a fed state.
Measured: AEs and clinically significant abnormal laboratory values will be recorded based upon investigator observation and subject reporting through a subject diary. Safety will be monitored by AEs, VS, physical exam, labs and ECGs during the study.
To examine the effects of SRT2104 (2.0 g administered once daily for 28 days) on reversing vasomotor and fibrinolytic dysfunction in both type 2 diabetes mellitus patients and otherwise healthy smokers in a fed state.
Measured: Forearm venous occlusion plethysmography will be performed on Days -1, 28, and 56 to assess vasomotor and fibrinolytic function. Pulse wave analysis and pulse wave velocity will be measured to assess arterial stiffness on Days -1, 28, and 56.
Secondary outcomes (4)
To investigate the effects of SRT2104 on the reduction of platelet activation markers (platelet-monocyte aggregates).
Measured: Serum/plasma/urine research sample(s) will be collected on Days 1, 28, and 56 and will be used to measure platelet activation (platelet-monocyte aggregates).
To evaluate SRT2104 effects on platelet and monocyte surface markers (P-selectin, CD11b), inflammatory markers (high sensitivity CRP, IL-6, SAA, TNF-α and sCD40L), and markers of oxidative stress (urinary and plasma F2-isoprostanes and nitrotyrosine).
Measured: Serum/plasma/urine research sample(s) will be collected on Days 1, 28, and 56 to evaluate platelet and monocyte surface markers, inflammatory markers, and markers of oxidative stress.
To characterize the pharmacokinetic profile of SRT2104 after a single dose and multiple administrations in both type 2 diabetes mellitus patients and otherwise healthy smokers in a fed state.
Measured: Plasma samples will be collected on Days 1, 28, and 56 at 0h, 15min, 30min, 1, 2, 3, 4, 8, and 12hrs post-dose. Samples will also be collected 24 and 27 hrs post-dose on Days 2, 29, and 57. Also, pre-dose samples will be collected on Days 15 and 43.
To explore the effects of SRT2104 on potential biomarkers of activity for glucose control (HbA1c, glycated albumin and fructosamine) and/or Sirt1 activation.
Measured: Serum/plasma/urine research sample(s) will be collected on Days 1, 28, and 56 and will be used to measure potential biomarkers of activity for glucose control.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2009 (estimated)
- Study start28 May 2010
- Primary completion12 Oct 2011
- Study completion12 Oct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- 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 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 38 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sirtris, a GSK Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- GSK Clinical Trials, Study director, GlaxoSmithKline
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01031108
- Sponsor's protocol ID
- 114089
- Status last verified
- Jun 2017
- First submitted
- 10 Dec 2009
- Last updated
- 20 Jun 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
Publications
Noh RM, Venkatasubramanian S, Daga S, Langrish J, Mills NL, Lang NN, Hoffmann E, Waterhouse B, Newby DE, Frier BM. Cardiometabolic effects of a novel SIRT1 activator, SRT2104, in people with type 2 diabetes mellitus. Open Heart. 2017 Sep 2;4(2):e000647. doi: 10.1136/openhrt-2017-000647. eCollection 2017.
PubMed 28912956Venkatasubramanian S, Noh RM, Daga S, Langrish JP, Mills NL, Waterhouse BR, Hoffmann E, Jacobson EW, Lang NN, Frier BM, Newby DE. Effects of the small molecule SIRT1 activator, SRT2104 on arterial stiffness in otherwise healthy cigarette smokers and subjects with type 2 diabetes mellitus. Open Heart. 2016 May 17;3(1):e000402. doi: 10.1136/openhrt-2016-000402. eCollection 2016.
PubMed 27239324Venkatasubramanian S, Noh RM, Daga S, Langrish JP, Joshi NV, Mills NL, Hoffmann E, Jacobson EW, Vlasuk GP, Waterhouse BR, Lang NN, Newby DE. Cardiovascular effects of a novel SIRT1 activator, SRT2104, in otherwise healthy cigarette smokers. J Am Heart Assoc. 2013 Jun 14;2(3):e000042. doi: 10.1161/JAHA.113.000042.
PubMed 23770971
Study at a glance
From the registry record, last updated by the sponsor on 20 Jun 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I, Randomized, Placebo-Controlled, Crossover Clinical Trial to Assess the Safety of Oral SRT2104 and Its Effects on Vascular Dysfunction in Otherwise Healthy Cigarette Smokers and Subjects With Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT01031108
- Acronym / sponsor ID
- 114089
- Conditions
- Diabetes Mellitus, Type 2
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 38 participants (actual)
- Lead sponsor
- Sirtris, a GSK CompanyIndustry (pharma, biotech, devices)
- Collaborators
- GlaxoSmithKline
- Study start
- 28 May 2010 (actual)
- Primary completion
- 12 Oct 2011 (actual)
- Study completion
- 12 Oct 2011 (actual)
- First posted
- 14 Dec 2009 (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.
The primary purpose of this study is to evaluate the safety and tolerability of SRT2104 (2.0 g administered once daily for 28 days) and to examine the effects of SRT2104 (2.0 g administered once daily for 28 days) on reversing vasomotor and fibrinolytic dysfunction in both type 2 diabetes mellitus patients and otherwise healthy cigarette smokers in a fed state.
This study will investigate the effects of SRT2104 on the reduction of platelet activation markers (platelet-monocyte aggregates), and to evaluate the effects of SRT2104 on platelet and monocyte surface markers (P-selectin, CD11b), inflammatory markers (high sensitivity CRP, IL-6, SAA, TNF-α and sCD40L), and markers of oxidative stress (urinary and plasma F2-isoprostanes and nitrotyrosine).
Further goals of this study is to characterize the pharmacokinetic profile of SRT2104 after a single dose and multiple administrations in both type 2 diabetes mellitus patients and otherwise healthy cigarette smokers in a fed state, and to explore the effects of SRT2104 on potential biomarkers of activity for glucose control (HbA1c, glycated albumin and fructosamine) and/or Sirt1 activation.
Detailed description
Single-center, randomized, double-blind, placebo-controlled, crossover, safety, activity, and pharmacokinetic (PK) study of 2.0 g of SRT2104 administered orally once daily for 28 consecutive days to two different populations: type 2 diabetic (T2D) subjects on an existing, stable, hypoglycemic regimen and otherwise healthy cigarette smokers (≥ 10cigarettes/day for at least 1 year). Approximately 24 subjects with T2D and 24 otherwise healthy cigarette smokers, aged 18-60 years, who fulfill the inclusion/exclusion criteria, will be enrolled in this study to ensure at least 20 evaluable subjects per population are enrolled. Subjects will be evenly stratified and randomized to receive SRT2104 2.0 g/day or placebo once daily for 28 days. After 28 days, subjects will cross over to receive the other test article for another 28 days of dosing, bringing the total dosing period to 56 days.
Subjects will sign the informed consent form at the screening visit (to occur within 21 days of first dose of test article), and will undergo screening assessments to verify eligibility for the study. If eligible and willing to participate, subjects will return to the clinic on Days -1 and 1 for safety assessments, hematology and biochemistry measurements, platelet monocyte aggregation (PMA) assessment, forearm venous occlusion plethysmography, pulse wave analysis (PWA), pulse wave velocity (PWV) and PK sampling. The first dose of test article will occur on Day 1 after eligibility has been confirmed. After each 28 day dosing period, subjects will return on Day 28 and Day 56 for safety assessments, hematology and biochemistry measurements, forearm plethysmography, PWA, PWV, and PK sampling. Subjects will return to the clinic on Days 2, 15, 29, 43, and 57 for safety assessments and additional PK sampling. Subjects will be asked to complete a study drug diary on a daily basis for compliance and adverse event (AE) monitoring (diabetic subjects will be required to monitor and record their fasting blood glucose in the diary also). An End of Study visit will occur 14 days following the final dose of SRT2104 or placebo on Day 70. A followup safety call will be made to each subject 30 days following their final dose of SRT2104 or placebo (Day 86).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Type 2 Diabetic Group | Other | Drug: Placebo, Drug: SRT2104The Type 2 Diabetic Treatment Group will be randomized to receive test material (2.0g SRT2104 or placebo) in the form of 8 capsules per day for 28 days. After 28 days of dosing, subjects will cross over to receive placebo or 2.0g SRT2104 for an additional 28 days. Dosing of SRT2104 or placebo will take place at approximately the same time every morning, approximately 15 minutes following consumption of a standardized morning meal (220 cc of Ensure Plus®). Subjects must wait at least 1-2 hours after dosing before consuming additional calories. Water is permitted ad libitum. |
| Otherwise Healthy Cigarette Smoking Group | Other | Drug: Placebo, Drug: SRT2104The Otherwise Healthy Cigarette Smoking Treatment Group will be randomized to receive test material (2.0g SRT2104 or placebo) in the form of 8 capsules per day for 28 days. After 28 days of dosing, subjects will cross over to receive placebo or 2.0g SRT2104 for an additional 28 days. Dosing of SRT2104 or placebo will take place at approximately the same time every morning, approximately 15 minutes following consumption of a standardized morning meal (220 cc of Ensure Plus®). Subjects must wait at least 1-2 hours after dosing before consuming additional calories. Water is permitted ad libitum. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Ambulatory male and female subjects (of any race) either with type 2 diabetes or otherwise healthy cigarette smokers (≥ 10 cigarettes/day for at least 1 year) within the age range of 18-70 years (inclusive) at the time of Screening.
- If a subject is diabetic, HbA1c at Screening is < 9.0%
- If a subject is diabetic, fasting plasma glucose (FPG) ≤ 13.875 mmol/L (≤ 250 mg/dL).
- If a subject is diabetic, an official diagnosis of type 2 diabetes must be documented for at least 6 months prior to first dose of test article.
- If a subject is diabetic, subject must be on an existing, stable, hypoglycemic therapy or a stable dietary regimen to control their disease for at least 3 months prior to Screening.
Key exclusion criteria (13 listed)
- If diabetic, any major illness in the past 3 months or any significant ongoing chronic medical illness not related to diabetes which in the opinion of the principal investigator or medical monitor could risk subject safety or interpretation of the results.
- If an otherwise healthy cigarette smoker, any major illness or injury in the past 3 months or any significant ongoing chronic medical illness (including diabetes) which in the opinion of the principal investigator or medical monitor could risk subject safety or interpretation of the results.
- Renal or liver impairment, defined as alkaline phosphatase and/or bilirubin ≥ 1.5 x ULN (an isolated bilirubin >1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin is <35%), serum creatinine level of ≥ 123.76 µmol/L (≥ 1.4 mg/dL ) in females and ≥ 132.60 µmol/L (≥ 1.5 mg/dL ) in males, and > 2 × ULN for liver transaminases (ALT and AST), respectively.
- History of or current gastrointestinal diseases or surgeries influencing drug absorption, except for appendectomy.
- History, within 3 years, of drug abuse (including benzodiazepines, opioids, amphetamine, cocaine, and THC).
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 |
|---|---|---|
| PlaceboFor the placebo product, SRT2104 drug substance will be replaced by microcrystalline cellulose (Avicel® PH 105) to match the SRT2104 investigational product. Eight placebo capsules are stored in a dosing bottle and provided to all participating subjects for oral ingestion. | Drug | Otherwise Healthy Cigarette Smoking Group, Type 2 Diabetic Group |
| SRT2104SRT2104 investigational product is a size 00 Swedish Orange opaque hard gelatin capsule containing 0.25 g of SRT2104, a new chemical entity which is supplied as a micronized, yellowish/amber powder. Eight SRT2104 capsules are stored in a dosing bottle and provided to all participating subjects for oral ingestion. | Drug | Otherwise Healthy Cigarette Smoking Group, Type 2 Diabetic Group |
Primary outcome
To evaluate the safety and tolerability of SRT2104 (2.0 g administered once daily for 28 days) in both type 2 diabetes mellitus patients and otherwise healthy cigarette smokers in a fed state.
Time frame: AEs and clinically significant abnormal laboratory values will be recorded based upon investigator observation and subject reporting through a subject diary. Safety will be monitored by AEs, VS, physical exam, labs and ECGs during the study.
To examine the effects of SRT2104 (2.0 g administered once daily for 28 days) on reversing vasomotor and fibrinolytic dysfunction in both type 2 diabetes mellitus patients and otherwise healthy smokers in a fed state.
Time frame: Forearm venous occlusion plethysmography will be performed on Days -1, 28, and 56 to assess vasomotor and fibrinolytic function. Pulse wave analysis and pulse wave velocity will be measured to assess arterial stiffness on Days -1, 28, and 56.
4 secondary outcomes
To investigate the effects of SRT2104 on the reduction of platelet activation markers (platelet-monocyte aggregates).
Time frame: Serum/plasma/urine research sample(s) will be collected on Days 1, 28, and 56 and will be used to measure platelet activation (platelet-monocyte aggregates).
To evaluate SRT2104 effects on platelet and monocyte surface markers (P-selectin, CD11b), inflammatory markers (high sensitivity CRP, IL-6, SAA, TNF-α and sCD40L), and markers of oxidative stress (urinary and plasma F2-isoprostanes and nitrotyrosine).
Time frame: Serum/plasma/urine research sample(s) will be collected on Days 1, 28, and 56 to evaluate platelet and monocyte surface markers, inflammatory markers, and markers of oxidative stress.
To characterize the pharmacokinetic profile of SRT2104 after a single dose and multiple administrations in both type 2 diabetes mellitus patients and otherwise healthy smokers in a fed state.
Time frame: Plasma samples will be collected on Days 1, 28, and 56 at 0h, 15min, 30min, 1, 2, 3, 4, 8, and 12hrs post-dose. Samples will also be collected 24 and 27 hrs post-dose on Days 2, 29, and 57. Also, pre-dose samples will be collected on Days 15 and 43.
To explore the effects of SRT2104 on potential biomarkers of activity for glucose control (HbA1c, glycated albumin and fructosamine) and/or Sirt1 activation.
Time frame: Serum/plasma/urine research sample(s) will be collected on Days 1, 28, and 56 and will be used to measure potential biomarkers of activity for glucose control.
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 20 Jun 2017.
- Derived from this study: PubMed 28912956Noh RM, Venkatasubramanian S, Daga S, Langrish J, Mills NL, Lang NN, Hoffmann E, Waterhouse B, Newby DE, Frier BM. Cardiometabolic effects of a novel SIRT1 activator, SRT2104, in people with type 2 diabetes mellitus. Open Heart. 2017 Sep 2;4(2):e000647. doi: 10.1136/openhrt-2017-000647. eCollection 2017.
- Derived from this study: PubMed 27239324Venkatasubramanian S, Noh RM, Daga S, Langrish JP, Mills NL, Waterhouse BR, Hoffmann E, Jacobson EW, Lang NN, Frier BM, Newby DE. Effects of the small molecule SIRT1 activator, SRT2104 on arterial stiffness in otherwise healthy cigarette smokers and subjects with type 2 diabetes mellitus. Open Heart. 2016 May 17;3(1):e000402. doi: 10.1136/openhrt-2016-000402. eCollection 2016.
- Derived from this study: PubMed 23770971Venkatasubramanian S, Noh RM, Daga S, Langrish JP, Joshi NV, Mills NL, Hoffmann E, Jacobson EW, Vlasuk GP, Waterhouse BR, Lang NN, Newby DE. Cardiovascular effects of a novel SIRT1 activator, SRT2104, in otherwise healthy cigarette smokers. J Am Heart Assoc. 2013 Jun 14;2(3):e000042. doi: 10.1161/JAHA.113.000042.
- Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.Link provided by the sponsor.
- Results for study 114089 can be found on the GSK Clinical Study Register.Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.
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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.
GSK Clinical Trials study director
GlaxoSmithKline
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing SRT2104 in people with Diabetes Mellitus, Type 2, run by Sirtris, a GSK Company at 1 site in United Kingdom.
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 19 inclusion and 13 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 20 Jun 2017. 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 United Kingdom. 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. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
To evaluate the safety and tolerability of SRT2104 (2.0 g administered once daily for 28 days) in both type 2 diabetes mellitus patients and otherwise healthy cigarette smokers in a fed state. (time frame: AEs and clinically significant abnormal laboratory values will be recorded based upon investigator observation and subject reporting through a subject diary. Safety will be monitored by AEs, VS, physical exam, labs and ECGs during the study.). The study lists 2 primary outcomes in all. 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 NCT01031108, which also lists 3 linked publications.
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 20 Jun 2017.