Type 1 Diabetes MellitusNCT00879710
Effect of Diabetes Mellitus on Cholesterol Metabolism
A study testing simvastatin or ezetimibe in people with Type 1 Diabetes Mellitus and Type 2 Diabetes Mellitus, run by Medical College of Wisconsin at 1 site in United States.
Trial summary
HMG CoA reductase inhibitors (statins) are commonly used to treat high cholesterol (HC) in both type 1 and type 2 diabetes mellitus (DM). Several studies have shown benefits of statin among patients of type 2 DM, however, no such data is available for patients with type 1 DM. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, Hypercholesterolemia
- What is being tested?
- simvastatin or ezetimibe
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 57 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2008to Jul 2013
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 1 DM:
- Age > 18 years
- Subjects diagnosed with type 1 DM (diagnosed based upon history of ketoacidosis, proven insulin dependence, absent C-peptide and or positive autoantibody profile (such as anti-GAD etc.)
- Stable A1C < 8.5%
- BMI < 31
- Type 2 DM:
Show all 10Show fewer
- Age > 18 years
- Subjects diagnosed with type II DM (diagnosed as adult onset, not-insulin dependent and not on insulin)
- Stable A1C < 8.5%
- BMI < 31
Who cannot join
- History of active, unstable cardiovascular disease (including MI, CHF, Stroke, Angina, CABG, stenting/PTCA, peripheral vascular disease, intermittent claudication)
- Pregnancy, nursing or likely to get pregnant during the course of the study (not on oral contraceptives and premenopausal)
- Chronic Kidney Disease (creatinine > 2.0)
- Liver function test abnormalities, not previously worked up (AST or ALT >4x upper limit of normal)
- Active substance abuse including alcohol
- History of severe Hypertriglyceridemia (untreated TG > 500) and on therapy
Show all 18Show fewer
- Use of agents that interfere with cholesterol absorption (such as fiber, resins etc.) which can not be discontinued for the duration of the study
- Actively enrolled in a weight loss program or following a special diet ( e.g.: Atkins diet)
- History of malignancy <5y
- History of Rhabdomyolysis and Myopathy
- Use of on-going oral corticosteroids
- History of HIV infection
- Use of following drugs/compounds: cyclosporine, itraconazole, ketoconazole, erythromycin, clarithromycin, HIV protease inhibitors, nefazodone, gemfibrozil, niacin, amiodarone, verapamil or large quantities of grape fruit juice (> 1 quart per day)
- Proteinuria: more than or equal to 300mg/24 hours calculated from random urine specimen.
- BMI >31
- Anyone with hypersensitivity to either one of the study medications
- Allergy to Soy bean products
- Unable to consume milk products with or without Lactaid®
Trial locations and contacts
1 site in 1 country.
United States1 site
Medical College of Wisconsin /Froedtert Hospital
Milwaukee, Wisconsin, 53226
About this study
Official title: Effect of Diabetes Mellitus on Cholesterol Absorption, Synthesis and Statin Efficacy
HMG CoA reductase inhibitors (statins) are commonly used to treat high cholesterol (HC) in both type 1 and type 2 diabetes mellitus (DM). Several studies have shown benefits of statin among patients of type 2 DM, however, no such data is available for patients with type 1 DM.
It is known from studies on cholesterol metabolism using surrogate markers that patients with type 1 DM have higher cholesterol absorption compared to normals and those with type 2 DM have higher cholesterol synthesis. Since statins inhibit synthesis, patients with type 1 DM may not have a good response and may respond better to cholesterol absorption inhibitors. The purpose of this study is to determine the cholesterol lowering effects of cholesterol absorption inhibitors and cholesterol synthesis inhibitors in subjects with type 1 and type 2 diabetes mellitus.
Read the detailed description
Hypothesis:
- Cholesterol absorption inhibitors like ezetimibe are more effective in lowering cholesterol in subjects with type 1 diabetes mellitus . The primary outcome measures are LDL cholesterol and cholesterol tracer absorption.
- Cholesterol synthesis inhibitors like statins are more effective in lowering cholesterol in subjects with type 2 diabetes mellitus. The primary outcomes are LDL cholesterol and 24 Hour urinary mevalonic acid levels.
- Response to statin is related to basal cholesterol synthesis rates. The primary outcomes are LDL cholesterol and 24 Hour urinary mevalonic acid levels.
- Response to ezetimibe is related to basal absorption rates. The primary outcome measures are LDL cholesterol, phytosterol levels and cholesterol tracer absorption.
Specific Aims:
- Measure baseline sterol absorption using plant sterol levels and and synthesis by using 24 h excretion of urinary mevalonic acid levels in type 1 and type 2 subjects
- Measure changes in lipid parameters, cholesterol synthesis and absorption markers in type 1 and type 2 subjects before and after 6 week therapy with simvastatin and 6 week therapy with ezetimibe after a 4 week washout period
- Start collecting blood for future genetic analysis for polymorphisms in cholesterol absorption genes
Specific Methods:
VISIT 1: Evaluation of all the subjects that are willing to participate in the study would be carried out at the GCRC until required sample size is recruited and will include the following:
- Sign informed consent
- Complete a health questionnaire that has a standardized format to collect basic information regarding past and current medical history
- Physical exam that includes measurement of blood pressure, height, weight, waist and hip circumference will be performed.
- Blood (30ml) would be drawn for baseline chemistry including creatinine, ALT, CPK, fasting lipid panel, Apo-B, Apo A1, glycated hemoglobin (HbA1c) and serum pregnancy test in women of child bearing age. Urine will be collected for urine analysis and presence of protein in the urine
- Evaluation of inclusion/exclusion criteria Subjects fulfilling the inclusion and exclusion criteria would be recruited into the study
Following specific procedures will be followed:
At the start of the study, subjects who are already on any lipid lowering medication will be asked to stop the medications 4 weeks prior to obtaining the baseline labs. No changes will be made to their diet, exercise pattern or in treatment for the DM. This will be done by a telephone conversation.
VISIT 2 (Day 1): Subjects will report fasting to GCRC at 8 AM. Subjects will briefly meet with bionutritionist for 24 hour dietary recall and instructions to keep a food diary on day 2 and 3. Blood sample (50ml) will be collected for fasting glucose, insulin, lipid panel, Apo B, Apo A-1, CPK, Hb A1c, plasma and serum frozen for sterol analyses (by GC) and WBC separated for DNA extraction.
The subject will be asked to consume with a cholesterol tracer (Cholesterol D5). Subjects will be asked to consume the 8 ounces in entirety. They will be asked not to eat/drink anything (except water) until the lunch time. If 8 Ounces are inadequate for breakfast, subjects will be offered another 8 Oz serving of Carnation® Instant Breakfast in the same or different flavor. If the subject is lactose intolerant, Lactaid tablets will be offered to offset the effects of milk. If subjects are unable to consume milk (with or without Lactaid®) or allergic to soy bean oil, they will be ineligible to participate in the study. Subjects will be sent home with a urine jug to collect 24-hour urine on day 3.
VISIT 3 (Day 4): Subject will bring the urine jug and food diary back for analysis and that same day will have blood (20ml) collected for evaluation of tracers. Food diary will be reviewed by the bionutritionist. Urine pregnancy test will be performed in women of child bearing age. Subjects will be started on either simvastatin or ezetimibe (we will alternate the subjects so that half the sample will initially be treated with simvastatin and half will be started on ezetimibe). The dose of Simvastatin (Merck) is 40 mg orally at nighttime for 6 weeks and the dose of ezetimibe (Schering-Plough) is 10 mg taken orally once a day. Subjects will be instructed on low-fat diet (therapeutic life style changes diet) recommended by American Heart Association by the bionutritionist.
VISIT 4 (Day 46 ± 7 days): Subjects will report fasting to GCRC at 8 AM. The subject will consume Carnation® Instant Breakfast with a cholesterol tracer (Cholesterol D5). Subjects will be asked to maintain same dietary restriction as visit 2. Subjects will be sent home with a urine jug to collect 24-hour urine on day 3. Subjects will start food diary on day 47 and 48.
VISIT 5 (Day 49 ± 7 days): Subject will bring the urine jug and food diary back for analysis and that same day will have blood (40ml) collected for evaluation of tracers, lipid panel, Apo A1, Apo B 100, ALT, CPK, plasma and serum stored for sterol analyses (by GC). Same day, weight, waist and hip circumference will be measured again. Food diary will be reviewed by bionutritionist. Subjects will be asked to bring back pill bottles also for pill count. Simvastatin or ezetimibe will be stopped for 4 weeks.
VISIT 6 (Day 77 ± 7 days): Subjects will be asked to come fasting to GCRC at 8 AM. 15ml of blood will be collected to measure lipid panel, apo B100 and Apo A1, Hb A1C, and ALT levels. Urine pregnancy test will be performed in women of child bearing age. Subjects will be started on 10 mg of ezetimibe or 40 mg of simvastatin as mentioned above for next 6 weeks.
VISIT 7 (Day 119 ± 7 days): Subjects will report fasting to GCRC at 8 AM. The subject will consume a Carnation® Instant Breakfast with cholesterol tracer (Cholesterol D5). Subjects will be asked to maintain same dietary restriction as visit 2. Subjects will be sent home with a urine jug to collect 24-hour urine on day 3.
Subjects will start food diary on day 120 and 121
VISIT 8 (Day 122 ± 7 days): Subject will bring the urine jug and food diary back for analysis and that same day will have blood (40 ml) collected for evaluation of tracers, lipid panel, Apo B100, Apo A1, Hb A1c, ALT, CPK, plasma and serum stored for sterol analyses (by GC). Weight, waist and hip circumference will be measured again. Food diary will be reviewed by bionutritionist. Ezetimibe or simvastatin therapy will be stopped. Subjects will be asked to resume their usual cholesterol lowering medications.
Ending the Study:
Study will be ended when all the required participants are enrolled. We will also consider stopping the study when accumulated data suggests that risks exceed benefits of the study or if preliminary data suggests there is a clear advantage of treating a particular group with a certain agent.
- Being tested
- simvastatin or ezetimibe
- Keywords
- Diabetes Mellitus, Hypercholesterolemia, Simvastatin, Ezetimibe.
- Medical subject headings
- Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2, Hypercholesterolemia, Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
simvastatin or ezetimibeDrug
Also called Zocor or Zetia
Subjects will be started on either simvastatin or ezetimibe (we will alternate the subjects so that half the sample will initially be treated with simvastatin and half will be started on ezetimibe). The dose of Simvastatin (Merck) is 40 mg orally at nighttime for 6 weeks and the dose of ezetimibe (Schering-Plough) is 10 mg taken orally once a day. Subjects will be instructed on low-fat diet (therapeutic life style changes diet) recommended by American Heart Association by the bionutritionist.
| Study group | Role | What they receive |
|---|---|---|
| Subjects with type 1 diabetes mellitus, option 1 | Other | Half the subjects will start with arm (i.e. every other subject in order)
* Simvastatin 40 mg tablet by month daily for 6 weeks,
* 4 weeks washout period
Half the subjects will start with arm (i.e. every other subject in order)
* Ezetimibe 10 mg by month for 6 weeks
* 4 weeks washout period
* Simvastatin 40 mg tablet by month daily for 6 weeks Receives: Drug: simvastatin or ezetimibe |
| Subjects with type 2 diabetes mellitus option 1 | Other | Half the subjects will start with arm (i.e. every other subject in order)
* Simvastatin 40 mg tablet by month daily for 6 weeks,
* 4 weeks washout period
Half the subjects will start with arm (i.e. every other subject in order)
* Ezetimibe 10 mg by month for 6 weeks
* 4 weeks washout period
* Simvastatin 40 mg tablet by month daily for 6 weeks Receives: Drug: simvastatin or ezetimibe |
| Subjects with type 1 diabetes mellitus, option 2 | Other | Half the subjects will start with arm (i.e. every other subject in order)
* Ezetimibe 10 mg by month for 6 weeks,
* 4 weeks washout period Receives: Drug: simvastatin or ezetimibe |
| Subjects with type 2 diabetes mellitus option 2 | Other | Half the subjects will start with arm (i.e. every other subject in order) Ezetimibe 10 mg by month for 6 weeks,
•4 weeks washout period Receives: Drug: simvastatin or ezetimibe |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in LDL Cholesterol
Subjects with T1DM or T2DM were assigned to alternating therapy with simvastatin (40 mg) or ezetimibe (10 mg) for 6 weeks in a crossover design.
The data are reported as follows.
Subjects with type 1 diabetes mellitus:
Simvastatin: Changes in LDL after 6-week therapy with simvastatin (irrespective of the treatment order) Ezetimibe: Changes in LDL after 6-week therapy with ezetimibe (irrespective of the treatment order)
Subjects with type 2 diabetes mellitus:
Simvastatin: Changes in LDL after 6-week therapy with simvastatin (irrespective of the treatment order) Ezetimibe: Changes in LDL after 6-week therapy with ezetimibe (irrespective of the treatment order)
Measured: 6 weeks after starting drug therapy
Secondary outcomes (1)
Changes in Cholesterol Absorption or Synthesis Rates From the Baseline
Our plan was to measure changes in cholesterol absorption and synthesis rates from the baseline after 6 weeks of statin or ezetimibe therapy.
Measured: 6 weeks after initiation of drug therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Apr 2009 (estimated)
- Study startAug 2008
- Primary completionJul 2013
- Study completionJul 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Type 1 Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Medical College of WisconsinThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 57 participants (actual)
Sponsor and investigators
- Lead sponsor
- Medical College of Wisconsin
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Srividya Kidambi, MD, Medical College of Wisconsin
- Investigators
- Srividya Kidambi, MD, Principal investigator, Medical College of WisconsinShailendra B Patel, MD, PhD, Principal investigator, Medical College of Wisconsin
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00879710
- Sponsor's protocol ID
- PRO00002485
- Status last verified
- Jul 2020
- First submitted
- 8 Apr 2009
- Last updated
- 29 Jul 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Ciriacks K, Coly G, Krishnaswami S, Patel SB, Kidambi S. Effects of simvastatin and ezetimibe in lowering low-density lipoprotein cholesterol in subjects with type 1 and type 2 diabetes mellitus. Metab Syndr Relat Disord. 2015 Mar;13(2):84-90. doi: 10.1089/met.2014.0114. Epub 2014 Dec 9.
PubMed 25490061
Study at a glance
From the registry record, last updated by the sponsor on 29 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Diabetes Mellitus on Cholesterol Absorption, Synthesis and Statin Efficacy
- ClinicalTrials.gov ID
- NCT00879710
- Acronym / sponsor ID
- PRO00002485
- Keywords
- Diabetes Mellitus, Hypercholesterolemia, Simvastatin, Ezetimibe.
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 57 participants (actual)
- Lead sponsor
- Medical College of WisconsinUniversity, hospital or other
- Study start
- Aug 2008
- Primary completion
- Jul 2013 (actual)
- Study completion
- Jul 2013 (actual)
- First posted
- 10 Apr 2009 (estimated)
- Results
- Posted 18 Apr 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
HMG CoA reductase inhibitors (statins) are commonly used to treat high cholesterol (HC) in both type 1 and type 2 diabetes mellitus (DM). Several studies have shown benefits of statin among patients of type 2 DM, however, no such data is available for patients with type 1 DM.
It is known from studies on cholesterol metabolism using surrogate markers that patients with type 1 DM have higher cholesterol absorption compared to normals and those with type 2 DM have higher cholesterol synthesis. Since statins inhibit synthesis, patients with type 1 DM may not have a good response and may respond better to cholesterol absorption inhibitors. The purpose of this study is to determine the cholesterol lowering effects of cholesterol absorption inhibitors and cholesterol synthesis inhibitors in subjects with type 1 and type 2 diabetes mellitus.
Detailed description
Hypothesis:
- Cholesterol absorption inhibitors like ezetimibe are more effective in lowering cholesterol in subjects with type 1 diabetes mellitus . The primary outcome measures are LDL cholesterol and cholesterol tracer absorption.
- Cholesterol synthesis inhibitors like statins are more effective in lowering cholesterol in subjects with type 2 diabetes mellitus. The primary outcomes are LDL cholesterol and 24 Hour urinary mevalonic acid levels.
- Response to statin is related to basal cholesterol synthesis rates. The primary outcomes are LDL cholesterol and 24 Hour urinary mevalonic acid levels.
- Response to ezetimibe is related to basal absorption rates. The primary outcome measures are LDL cholesterol, phytosterol levels and cholesterol tracer absorption.
Specific Aims:
- Measure baseline sterol absorption using plant sterol levels and and synthesis by using 24 h excretion of urinary mevalonic acid levels in type 1 and type 2 subjects
- Measure changes in lipid parameters, cholesterol synthesis and absorption markers in type 1 and type 2 subjects before and after 6 week therapy with simvastatin and 6 week therapy with ezetimibe after a 4 week washout period
- Start collecting blood for future genetic analysis for polymorphisms in cholesterol absorption genes
Specific Methods:
VISIT 1: Evaluation of all the subjects that are willing to participate in the study would be carried out at the GCRC until required sample size is recruited and will include the following:
- Sign informed consent
- Complete a health questionnaire that has a standardized format to collect basic information regarding past and current medical history
- Physical exam that includes measurement of blood pressure, height, weight, waist and hip circumference will be performed.
- Blood (30ml) would be drawn for baseline chemistry including creatinine, ALT, CPK, fasting lipid panel, Apo-B, Apo A1, glycated hemoglobin (HbA1c) and serum pregnancy test in women of child bearing age. Urine will be collected for urine analysis and presence of protein in the urine
- Evaluation of inclusion/exclusion criteria Subjects fulfilling the inclusion and exclusion criteria would be recruited into the study
Following specific procedures will be followed:
At the start of the study, subjects who are already on any lipid lowering medication will be asked to stop the medications 4 weeks prior to obtaining the baseline labs. No changes will be made to their diet, exercise pattern or in treatment for the DM. This will be done by a telephone conversation.
VISIT 2 (Day 1): Subjects will report fasting to GCRC at 8 AM. Subjects will briefly meet with bionutritionist for 24 hour dietary recall and instructions to keep a food diary on day 2 and 3. Blood sample (50ml) will be collected for fasting glucose, insulin, lipid panel, Apo B, Apo A-1, CPK, Hb A1c, plasma and serum frozen for sterol analyses (by GC) and WBC separated for DNA extraction.
The subject will be asked to consume with a cholesterol tracer (Cholesterol D5). Subjects will be asked to consume the 8 ounces in entirety. They will be asked not to eat/drink anything (except water) until the lunch time. If 8 Ounces are inadequate for breakfast, subjects will be offered another 8 Oz serving of Carnation® Instant Breakfast in the same or different flavor. If the subject is lactose intolerant, Lactaid tablets will be offered to offset the effects of milk. If subjects are unable to consume milk (with or without Lactaid®) or allergic to soy bean oil, they will be ineligible to participate in the study. Subjects will be sent home with a urine jug to collect 24-hour urine on day 3.
VISIT 3 (Day 4): Subject will bring the urine jug and food diary back for analysis and that same day will have blood (20ml) collected for evaluation of tracers. Food diary will be reviewed by the bionutritionist. Urine pregnancy test will be performed in women of child bearing age. Subjects will be started on either simvastatin or ezetimibe (we will alternate the subjects so that half the sample will initially be treated with simvastatin and half will be started on ezetimibe). The dose of Simvastatin (Merck) is 40 mg orally at nighttime for 6 weeks and the dose of ezetimibe (Schering-Plough) is 10 mg taken orally once a day. Subjects will be instructed on low-fat diet (therapeutic life style changes diet) recommended by American Heart Association by the bionutritionist.
VISIT 4 (Day 46 ± 7 days): Subjects will report fasting to GCRC at 8 AM. The subject will consume Carnation® Instant Breakfast with a cholesterol tracer (Cholesterol D5). Subjects will be asked to maintain same dietary restriction as visit 2. Subjects will be sent home with a urine jug to collect 24-hour urine on day 3. Subjects will start food diary on day 47 and 48.
VISIT 5 (Day 49 ± 7 days): Subject will bring the urine jug and food diary back for analysis and that same day will have blood (40ml) collected for evaluation of tracers, lipid panel, Apo A1, Apo B 100, ALT, CPK, plasma and serum stored for sterol analyses (by GC). Same day, weight, waist and hip circumference will be measured again. Food diary will be reviewed by bionutritionist. Subjects will be asked to bring back pill bottles also for pill count. Simvastatin or ezetimibe will be stopped for 4 weeks.
VISIT 6 (Day 77 ± 7 days): Subjects will be asked to come fasting to GCRC at 8 AM. 15ml of blood will be collected to measure lipid panel, apo B100 and Apo A1, Hb A1C, and ALT levels. Urine pregnancy test will be performed in women of child bearing age. Subjects will be started on 10 mg of ezetimibe or 40 mg of simvastatin as mentioned above for next 6 weeks.
VISIT 7 (Day 119 ± 7 days): Subjects will report fasting to GCRC at 8 AM. The subject will consume a Carnation® Instant Breakfast with cholesterol tracer (Cholesterol D5). Subjects will be asked to maintain same dietary restriction as visit 2. Subjects will be sent home with a urine jug to collect 24-hour urine on day 3.
Subjects will start food diary on day 120 and 121
VISIT 8 (Day 122 ± 7 days): Subject will bring the urine jug and food diary back for analysis and that same day will have blood (40 ml) collected for evaluation of tracers, lipid panel, Apo B100, Apo A1, Hb A1c, ALT, CPK, plasma and serum stored for sterol analyses (by GC). Weight, waist and hip circumference will be measured again. Food diary will be reviewed by bionutritionist. Ezetimibe or simvastatin therapy will be stopped. Subjects will be asked to resume their usual cholesterol lowering medications.
Ending the Study:
Study will be ended when all the required participants are enrolled. We will also consider stopping the study when accumulated data suggests that risks exceed benefits of the study or if preliminary data suggests there is a clear advantage of treating a particular group with a certain agent.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Subjects with type 1 diabetes mellitus, option 1 | Other | Drug: simvastatin or ezetimibeHalf the subjects will start with arm (i.e. every other subject in order) * Simvastatin 40 mg tablet by month daily for 6 weeks, * 4 weeks washout period Half the subjects will start with arm (i.e. every other subject in order) * Ezetimibe 10 mg by month for 6 weeks * 4 weeks washout period * Simvastatin 40 mg tablet by month daily for 6 weeks |
| Subjects with type 2 diabetes mellitus option 1 | Other | Drug: simvastatin or ezetimibeHalf the subjects will start with arm (i.e. every other subject in order) * Simvastatin 40 mg tablet by month daily for 6 weeks, * 4 weeks washout period Half the subjects will start with arm (i.e. every other subject in order) * Ezetimibe 10 mg by month for 6 weeks * 4 weeks washout period * Simvastatin 40 mg tablet by month daily for 6 weeks |
| Subjects with type 1 diabetes mellitus, option 2 | Other | Drug: simvastatin or ezetimibeHalf the subjects will start with arm (i.e. every other subject in order) * Ezetimibe 10 mg by month for 6 weeks, * 4 weeks washout period |
| Subjects with type 2 diabetes mellitus option 2 | Other | Drug: simvastatin or ezetimibeHalf the subjects will start with arm (i.e. every other subject in order) Ezetimibe 10 mg by month for 6 weeks, •4 weeks washout period |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Type 1 DM:
- Age > 18 years
- Subjects diagnosed with type 1 DM (diagnosed based upon history of ketoacidosis, proven insulin dependence, absent C-peptide and or positive autoantibody profile (such as anti-GAD etc.)
- Stable A1C < 8.5%
- BMI < 31
Key exclusion criteria (18 listed)
- History of active, unstable cardiovascular disease (including MI, CHF, Stroke, Angina, CABG, stenting/PTCA, peripheral vascular disease, intermittent claudication)
- Pregnancy, nursing or likely to get pregnant during the course of the study (not on oral contraceptives and premenopausal)
- Chronic Kidney Disease (creatinine > 2.0)
- Liver function test abnormalities, not previously worked up (AST or ALT >4x upper limit of normal)
- Active substance abuse including alcohol
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 |
|---|---|---|
| simvastatin or ezetimibeAlso: Zocor or ZetiaSubjects will be started on either simvastatin or ezetimibe (we will alternate the subjects so that half the sample will initially be treated with simvastatin and half will be started on ezetimibe). The dose of Simvastatin (Merck) is 40 mg orally at nighttime for 6 weeks and the dose of ezetimibe (Schering-Plough) is 10 mg taken orally once a day. Subjects will be instructed on low-fat diet (therapeutic life style changes diet) recommended by American Heart Association by the bionutritionist. | Drug | Subjects with type 1 diabetes mellitus, option 1, Subjects with type 1 diabetes mellitus, option 2, Subjects with type 2 diabetes mellitus option 1, Subjects with type 2 diabetes mellitus option 2 |
Primary outcome
Changes in LDL Cholesterol
Time frame: 6 weeks after starting drug therapy
Subjects with T1DM or T2DM were assigned to alternating therapy with simvastatin (40 mg) or ezetimibe (10 mg) for 6 weeks in a crossover design. The data are reported as follows. Subjects with type 1 diabetes mellitus: Simvastatin: Changes in LDL after 6-week therapy with simvastatin (irrespective of the treatment order) Ezetimibe: Changes in LDL after 6-week therapy with ezetimibe (irrespective of the treatment order) Subjects with type 2 diabetes mellitus: Simvastatin: Changes in LDL after 6-week therapy with simvastatin (irrespective of the treatment order) Ezetimibe: Changes in LDL after 6-week therapy with ezetimibe (irrespective of the treatment order)
1 secondary outcome
Changes in Cholesterol Absorption or Synthesis Rates From the Baseline
Time frame: 6 weeks after initiation of drug therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jul 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25490061Ciriacks K, Coly G, Krishnaswami S, Patel SB, Kidambi S. Effects of simvastatin and ezetimibe in lowering low-density lipoprotein cholesterol in subjects with type 1 and type 2 diabetes mellitus. Metab Syndr Relat Disord. 2015 Mar;13(2):84-90. doi: 10.1089/met.2014.0114. Epub 2014 Dec 9.
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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.
Srividya Kidambi, MD principal investigator
Medical College of Wisconsin
Shailendra B Patel, MD, PhD principal investigator
Medical College of Wisconsin
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing simvastatin or ezetimibe in people with Type 1 Diabetes Mellitus and Type 2 Diabetes Mellitus, run by Medical College of Wisconsin at 1 site in United States.
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 10 inclusion and 18 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 29 Jul 2020. 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 States. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Apr 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Changes in LDL Cholesterol (time frame: 6 weeks after starting drug therapy). 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 NCT00879710, 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 29 Jul 2020.