Trial Outcomes & Findings for Effect of Diabetes Mellitus on Cholesterol Metabolism (NCT NCT00879710)

Last Updated: 2020-07-29

Results Overview

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)

Recruitment status

COMPLETED

Study phase

Target enrollment

57 participants

Primary outcome timeframe

6 weeks after starting drug therapy

Results posted on

2020-07-29

Participant Flow

Subjects were recruited by advertising in local news papers, Craig's list, local clinics between 2007 and 2012. Subjects were initially screened over the phone by using a telephone screening criteria (n=549). And eligible subjects (n=86) were brought to Translational Research Units (previously GCRC) for a screening visit of which 57 were enrolled.

After screening visit, 23 patients with type 1 diabetes, and 34 patients with type 2 diabetes were enrolled. All the subjects were asked to stop their lipid lowering medications for 4 weeks. All the subjects who were enrolled started the study.

Participant milestones

Participant milestones
Measure	Subjects With Type 1 Diabetes mellitus_Simva_Ezet Subjects with T1DM were ascertained based on ketosis at the time of diagnosis and/or being treated with insulin since the diagnosis. All subjects were interviewed by S.K. (a board certified endocrinologist) to ensure classifications of T1DM and T2DM were accurate by history and physical exam. This group started with simvastatin for 6 weeks followed by 4 week washout. They were then placed on 6 weeks of ezetimibe.	Subjects With Type 2 Diabetes mellitus_Simva_Ezet Patients with T2DM were treated only with oral sulfonylurea drugs and/or biguanides and/or thiazolidinediones. Subjects with T2DM were excluded if they were on insulin or other injectable agents. All subjects were interviewed by S.K. to ensure classifications of T1DM and T2DM were accurate by history. This group started with simvastatin for 6 weeks followed by 4 week washout. They were then placed on 6 weeks of ezetimibe.	Subjects With Type 1 Diabetes mellitus_Ezet_Simva Subjects with T1DM were ascertained based on ketosis at the time of diagnosis and/or being treated with insulin since the diagnosis. All subjects were interviewed by S.K. (a board certified endocrinologist) to ensure classifications of T1DM and T2DM were accurate by history and physical exam. This group started with ezetimibe for 6 weeks followed by 4 week washout. They were then placed on 6 weeks of simvastatin.	Subjects With Type 2 Diabetes mellitus_Ezet_Simva Patients with T2DM were treated only with oral sulfonylurea drugs and/or biguanides and/or thiazolidinediones. Subjects with T2DM were excluded if they were on insulin or other injectable agents. All subjects were interviewed by S.K. to ensure classifications of T1DM and T2DM were accurate by history. This group started with ezetimibe for 6 weeks followed by 4 week washout. They were then placed on 6 weeks of simvastatin.
Phase 1 - 6 Weeks STARTED	12	17	11	17
Phase 1 - 6 Weeks COMPLETED	10	14	9	13
Phase 1 - 6 Weeks NOT COMPLETED	2	3	2	4
Wash Out Period of 4 Weeks STARTED	10	14	10	13
Wash Out Period of 4 Weeks COMPLETED	10	14	10	13
Wash Out Period of 4 Weeks NOT COMPLETED	0	0	0	0
Phase 2 6 Weeks STARTED	10	14	10	13
Phase 2 6 Weeks COMPLETED	10	14	10	13
Phase 2 6 Weeks NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Subjects With Type 1 Diabetes mellitus_Simva_Ezet Subjects with T1DM were ascertained based on ketosis at the time of diagnosis and/or being treated with insulin since the diagnosis. All subjects were interviewed by S.K. (a board certified endocrinologist) to ensure classifications of T1DM and T2DM were accurate by history and physical exam. This group started with simvastatin for 6 weeks followed by 4 week washout. They were then placed on 6 weeks of ezetimibe.	Subjects With Type 2 Diabetes mellitus_Simva_Ezet Patients with T2DM were treated only with oral sulfonylurea drugs and/or biguanides and/or thiazolidinediones. Subjects with T2DM were excluded if they were on insulin or other injectable agents. All subjects were interviewed by S.K. to ensure classifications of T1DM and T2DM were accurate by history. This group started with simvastatin for 6 weeks followed by 4 week washout. They were then placed on 6 weeks of ezetimibe.	Subjects With Type 1 Diabetes mellitus_Ezet_Simva Subjects with T1DM were ascertained based on ketosis at the time of diagnosis and/or being treated with insulin since the diagnosis. All subjects were interviewed by S.K. (a board certified endocrinologist) to ensure classifications of T1DM and T2DM were accurate by history and physical exam. This group started with ezetimibe for 6 weeks followed by 4 week washout. They were then placed on 6 weeks of simvastatin.	Subjects With Type 2 Diabetes mellitus_Ezet_Simva Patients with T2DM were treated only with oral sulfonylurea drugs and/or biguanides and/or thiazolidinediones. Subjects with T2DM were excluded if they were on insulin or other injectable agents. All subjects were interviewed by S.K. to ensure classifications of T1DM and T2DM were accurate by history. This group started with ezetimibe for 6 weeks followed by 4 week washout. They were then placed on 6 weeks of simvastatin.
Phase 1 - 6 Weeks Lost to Follow-up	2	3	1	4
Phase 1 - 6 Weeks Adverse Event	0	0	1	0

Baseline Characteristics

Effect of Diabetes Mellitus on Cholesterol Metabolism

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Subjects With Type 1 Diabetes Mellitus, n=23 Participants * Simvastatin 40 mg tablet by month daily for 6 weeks, * 4 weeks washout period * Ezetimibe 10 mg by month for 6 weeks simvastatin: Subjects will be started on eithersimvastatin 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.	Subjects With Type 2 Diabetes Mellitus n=34 Participants * Simvastatin 40 mg tablet by month daily for 6 weeks, * 4 weeks washout period * Ezetimibe 10 mg by month for 6 weeks simvastatin: Subjects will be started on eithersimvastatin 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.	Total n=57 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	19 Participants n=5 Participants	22 Participants n=7 Participants	41 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	12 Participants n=7 Participants	16 Participants n=5 Participants
Age, Continuous	49 years STANDARD_DEVIATION 13 • n=5 Participants	65 years STANDARD_DEVIATION 10 • n=7 Participants	57 years STANDARD_DEVIATION 12 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	18 Participants n=7 Participants	29 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	16 Participants n=7 Participants	28 Participants n=5 Participants
Region of Enrollment United States	23 participants n=5 Participants	34 participants n=7 Participants	57 participants n=5 Participants

PRIMARY outcome

Timeframe: 6 weeks after starting drug therapy

Population: We did not reach our target inclusion criteria, sample size calculations were based on assumptions. Our analyses after 3 years of data collection showed that we had adequate sample to answer the question we were asking. Study was terminated after 3 years with further lack of funds. Planned statistical analyses was conducted.

Outcome measures

Outcome measures
Measure	Subjects With Type 1 Diabetes Mellitus, n=20 Participants * Simvastatin 40 mg tablet by month daily for 6 weeks, * 4 weeks washout period * Ezetimibe 10 mg by month for 6 weeks simvastatin: Subjects will be started on eithersimvastatin 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.	Subjects With Type 2 Diabetes Mellitus n=27 Participants * Simvastatin 40 mg tablet by month daily for 6 weeks, * 4 weeks washout period * Ezetimibe 10 mg by month for 6 weeks simvastatin: Subjects will be started on eithersimvastatin 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.
Changes in LDL Cholesterol simvastatin	-0.83 mmol/L Standard Error 0.24	-1.47 mmol/L Standard Error 0.19
Changes in LDL Cholesterol ezetimibe	-0.93 mmol/L Standard Error 0.23	-0.32 mmol/L Standard Error 0.19

SECONDARY outcome

Timeframe: 6 weeks after initiation of drug therapy

Population: Secondary analyses were not conducted in any subjects. This is due to lack of funds.

Our plan was to measure changes in cholesterol absorption and synthesis rates from the baseline after 6 weeks of statin or ezetimibe therapy.

Outcome measures

Outcome data not reported

Adverse Events

Subjects With Type 1 Diabetes Mellitus

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Subjects With Type 2 Diabetes Mellitus

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Subjects With Type 1 Diabetes Mellitus n=20 participants at risk * Simvastatin 40 mg tablet/ezetimibe 10 mg by mouth daily for 6 weeks, * 4 weeks washout period in between 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.	Subjects With Type 2 Diabetes Mellitus n=27 participants at risk * Simvastatin 40 mg tablet/ezetimibe 10 mg by mouth daily for 6 weeks, * 4 weeks washout period in between 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.
General disorders Intense sweating and dizziness lasting 1 hour with ezetimibe	5.0% 1/20 • Number of events 1 • Adverse event data was collected for 16 weeks (time during which participants were in the study). 16 weeks 6 weeks of simvastatin or ezetimibe 4 weeks washout 6 weeks of simvastatin or ezetimibe	0.00% 0/27 • Adverse event data was collected for 16 weeks (time during which participants were in the study). 16 weeks 6 weeks of simvastatin or ezetimibe 4 weeks washout 6 weeks of simvastatin or ezetimibe

Additional Information

Srividya Kidambi, MD, MS

Medical College of Wisconsin

Phone: 414-955-4843

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place