Effect of Diabetes Mellitus on Cholesterol Metabolism

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Srividya Kidambi, MD, Medical College of Wisconsin
ClinicalTrials.gov Identifier:
NCT00879710
First received: April 8, 2009
Last updated: March 16, 2016
Last verified: March 2016
Results First Received: August 25, 2015  
Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Endpoint Classification: Efficacy Study;   Intervention Model: Crossover Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Type 1 Diabetes Mellitus
Type 2 Diabetes Mellitus
Hypercholesterolemia
Intervention: Drug: simvastatin or ezetimibe

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
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.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment

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.


Reporting Groups
  Description
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.


Participant Flow for 3 periods

Period 1:   Phase 1 - 6 Weeks
    Subjects With Type 1 Diabetes mellitus_Simva_Ezet     Subjects With Type 2 Diabetes mellitus_Simva_Ezet     Subjects With Type 1 Diabetes mellitus_Ezet_Simva     Subjects With Type 2 Diabetes mellitus_Ezet_Simva  
STARTED     12 [1]   17 [1]   11 [2]   17 [2]
COMPLETED     10     14     9     13  
NOT COMPLETED     2     3     2     4  
Lost to Follow-up                 2                 3                 1                 4  
Adverse Event                 0                 0                 1                 0  
[1] Started with simvastatin 40 mg as the starting drug
[2] Started with ezetimibe 10 mg as the starting drug

Period 2:   Wash Out Period of 4 Weeks
    Subjects With Type 1 Diabetes mellitus_Simva_Ezet     Subjects With Type 2 Diabetes mellitus_Simva_Ezet     Subjects With Type 1 Diabetes mellitus_Ezet_Simva     Subjects With Type 2 Diabetes mellitus_Ezet_Simva  
STARTED     10     14     10 [1]   13  
COMPLETED     10     14     10     13  
NOT COMPLETED     0     0     0     0  
[1] The person who did not complete ezetimibe arm came back to complete simvastatin arm.

Period 3:   Phase 2 6 Weeks
    Subjects With Type 1 Diabetes mellitus_Simva_Ezet     Subjects With Type 2 Diabetes mellitus_Simva_Ezet     Subjects With Type 1 Diabetes mellitus_Ezet_Simva     Subjects With Type 2 Diabetes mellitus_Ezet_Simva  
STARTED     10     14     10     13  
COMPLETED     10     14     10     13  
NOT COMPLETED     0     0     0     0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Subjects With Type 1 Diabetes Mellitus,
  • 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
  • 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 Total of all reporting groups

Baseline Measures
    Subjects With Type 1 Diabetes Mellitus,     Subjects With Type 2 Diabetes Mellitus     Total  
Number of Participants  
[units: participants]
  23     34     57  
Age  
[units: participants]
     
<=18 years     0     0     0  
Between 18 and 65 years     19     22     41  
>=65 years     4     12     16  
Age  
[units: years]
Mean (Standard Deviation)
  49  (13)     65  (10)     57  (12)  
Gender  
[units: participants]
     
Female     11     18     29  
Male     12     16     28  
Region of Enrollment  
[units: participants]
     
United States     23     34     57  



  Outcome Measures

1.  Primary:   Changes in LDL Cholesterol   [ Time Frame: 6 weeks after starting drug therapy ]

2.  Secondary:   Changes in Cholesterol Absorption or Synthesis Rates From the Baseline   [ Time Frame: 6 weeks after initiation of drug therapy ]
Results not yet reported.   Anticipated Reporting Date:   No text entered.   Safety Issue:   No


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
  1. Smaller than desirable sample size due to difficulty in recruitment.
  2. Could not evaluate the effect of duration of the diabetes mellitus as independent confirmation of the duration could not be done.
  3. Apolipoprotein levels were not measured.


  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Srividya Kidambi, MD, MS
Organization: Medical College of Wisconsin
phone: 414-955-4843
e-mail: skidambi@mcw.edu


Publications of Results:

Responsible Party: Srividya Kidambi, MD, Medical College of Wisconsin
ClinicalTrials.gov Identifier: NCT00879710     History of Changes
Other Study ID Numbers: PRO00002485
Study First Received: April 8, 2009
Results First Received: August 25, 2015
Last Updated: March 16, 2016
Health Authority: United States: Institutional Review Board