NCT00879710

Brief 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. 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
57

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Aug 2008

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

August 1, 2008

Completed
8 months until next milestone

First Submitted

Initial submission to the registry

April 8, 2009

Completed
2 days until next milestone

First Posted

Study publicly available on registry

April 10, 2009

Completed
4.2 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2013

Completed
2.8 years until next milestone

Results Posted

Study results publicly available

April 18, 2016

Completed
Last Updated

July 29, 2020

Status Verified

July 1, 2020

Enrollment Period

4.9 years

First QC Date

April 8, 2009

Results QC Date

August 25, 2015

Last Update Submit

July 13, 2020

Conditions

Type 1 Diabetes MellitusType 2 Diabetes MellitusHypercholesterolemia

Keywords

Diabetes MellitusHypercholesterolemiaSimvastatinEzetimibe.

Outcome Measures

Primary Outcomes (1)

  • 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)

    6 weeks after starting drug therapy

Secondary Outcomes (1)

  • Changes in Cholesterol Absorption or Synthesis Rates From the Baseline

    6 weeks after initiation of drug therapy

Study Arms (4)

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

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

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

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

Drug: simvastatin or ezetimibe

Interventions

simvastatin or ezetimibeDRUG

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.

Also known as: Zocor or Zetia
Subjects with type 1 diabetes mellitus, option 1Subjects with type 1 diabetes mellitus, option 2Subjects with type 2 diabetes mellitus option 1Subjects with type 2 diabetes mellitus option 2

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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:
  • 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

You may not qualify if:

  • 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
  • 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
  • +3 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Medical College of Wisconsin /Froedtert Hospital

Milwaukee, Wisconsin, 53226, United States

Location

Related Publications (1)

  • 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.

    PMID: 25490061RESULT

MeSH Terms

Conditions

Diabetes Mellitus, Type 1Diabetes Mellitus, Type 2HypercholesterolemiaDiabetes Mellitus

Interventions

SimvastatinEzetimibe

Condition Hierarchy (Ancestors)

Glucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesAutoimmune DiseasesImmune System DiseasesHyperlipidemiasDyslipidemiasLipid Metabolism Disorders

Intervention Hierarchy (Ancestors)

LovastatinNaphthalenesPolycyclic Aromatic HydrocarbonsHydrocarbons, AromaticHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsPolycyclic CompoundsAzetidinesAzetinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Limitations and Caveats

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.

Results Point of Contact

Title
Srividya Kidambi, MD, MS
Organization
Medical College of Wisconsin
skidambi@mcw.edu
414-955-4843

Study Officials

  • Srividya Kidambi, MD

    Medical College of Wisconsin

    PRINCIPAL INVESTIGATOR

  • Shailendra B Patel, MD, PhD

    Medical College of Wisconsin

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor, Endocrinology

Study Record Dates

First Submitted

April 8, 2009

First Posted

April 10, 2009

Study Start

August 1, 2008

Primary Completion

July 1, 2013

Study Completion

July 1, 2013

Last Updated

July 29, 2020

Results First Posted

April 18, 2016

Record last verified: 2020-07

Locations

US(1)