Clinical Trial of Zocor (Simvastatin) and Vytorin (Ezetimibe/Simvastatin) in Adolescents With Type 1 Diabetes

• Sponsor: University of Colorado, Denver (Other)
• Overall Status: Completed
• CT.gov ID: NCT00477204
• Collaborator: Merck Sharp & Dohme LLC (Industry), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 9
• Location: 1
• Arms: 2
• Duration (Months): 39
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of the study is to establish the safety of ezetimibe/simvastatin and simvastatin in adolescents with Type 1 Diabetes and to determine the amount of decrease in LDL-cholesterol.The study hypothesizes that simvastatin and ezetimibe/simvastatin will be safe in adolescents with Type 1 Diabetes and will lower LDL-cholesterol at 6 months.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes Mellitus; Dyslipidemia	Drug: Simvastatin; Drug: Ezetimibe/Simvastatin	Phase 2

Detailed Description

Cardiovascular disease is the leading cause of death in people with type 1 diabetes mellitus (T1DM) and since atherosclerosis begins in childhood, data to inform clinicians as to appropriate dyslipidemia treatment in this high-risk population are of great public health importance. In this trial of lipid-lowering medications (Zocor [simvastatin], a statin, compared to Vytorin [ezetimibe/simvastatin], a combination of a statin and Zetia, a medication that blocks cholesterol absorption) will be performed in patients ages 12-18 years with LDL ≥ 130 mg/dl, consistent with current ADA guidelines. The study hypothesizes that Zocor and Vytorin will be safe in adolescents with T1DM and will lower LDL-cholesterol at 6 months compared to baseline. In a two-arm design, Vytorin will lower LDL-c more than monotherapy with Zocor.

Study Design

• Study Type: Interventional
• Actual Enrollment: 9 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Clinical Trial of Zocor and Vytorin in Adolescents With Type 1 Diabetes
• Study Start Date: May 1, 2007
• Actual Primary Completion Date: Aug 1, 2010
• Actual Study Completion Date: Aug 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Simvastatin Zocor(simvastatin)(20 mg)daily for 6 months along with Placebo (sugar pill)of active comparator (Vytorin [simvastatin] + Zetia [ezetimibe].	Drug: Simvastatin; simvastatin 20 mg daily; Other Names: Zocor
Active Comparator: Ezetimibe/Simvastatin Vytorin(simvastatin [Zocor} + ezetimibe [Zetia])(20 mg)daily for 6 months along with placebo (sugar pill)of comparator (Vytorin [simvastatin]).	Drug: Ezetimibe/Simvastatin; Ezetimibe (10mg)/Simvastatin (20mg); Other Names: Vytorin

Outcome Measures

Primary Outcome Measures

1. Change in LDL-c From Baseline to 6 Months in Subjects With Type 1 Diabetes Taking Vytorin or Zocor. [Baseline to 6 months]

   Change in LDL-c between Zocor and Vytorin treatment in subjects with Type 1 Diabetes measured at baseline to the 6-month study visit.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 12 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 12-18 years of age with Type 1 Diabetes and seen at the Barbara Davis Center for Childhood Diabetes

• Positive diabetes auto-antibodies or provider diagnosed Type 1 Diabetes

• LDL > 130 mg/dl.

Exclusion Criteria:

• Familial hypercholesterolemia, Triglycerides (TG) > 400mg/dl

• Type 1 Diabetes of less than three-month duration

• HbA1c>9.5%

• Abnormal thyroid function

• Abnormal Creatine Kinase (CK) values (defined as > 10 times the upper limit of normal)

• Abnormal liver function tests (ALT/AST) (defined as >3 times the upper limit of normal)

• Pregnancy, and patients on oral contraceptives

• All resources are in English. Spanish speakers will not be available for the follow-up calls.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Barbara Davis Center for Childhood Diabetes	Aurora	Colorado	United States	80045

Sponsors and Collaborators

• University of Colorado, Denver
• Merck Sharp & Dohme LLC
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: David M Maahs, MD, University of Colorado, Denver
• Principal Investigator: R. P Wadwa, MD, University of Colorado, Denver

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Colorado, Denver
• ClinicalTrials.gov Identifier: NCT00477204
• Other Study ID Numbers: 06-1036; K23DK075360
• First Posted: May 22, 2007
• Last Update Posted: Nov 10, 2020
• Last Verified: Oct 1, 2020

• Keywords provided by University of Colorado, Denver: Type 1 Diabetes Mellitus; dyslipidemia; adolescents
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 1; Dyslipidemias; Simvastatin; Ezetimibe; Ezetimibe, Simvastatin Drug Combination

Study Results

Participant Flow

Recruitment Details	Dates of recruitment: baseline 12/20/07-2/9/10; all participants completed 6-month trial by 8/3/10. All study participants seen at a medical clinic in an area designated for clinical research.
Pre-assignment Detail	We identified 105 potential subjects. Of these, 42 patients proved to be ineligible, 26 declined invitation to a screening visit, 16 were not able to be scheduled, and 3 were interested but ineligible for the study. Therefore, 18 agreed to be in the study and 17 subjects attended a study screening visit of which 9 were enrolled in the study.

Arm/Group Title	Ezetimibe/Simvastatin	Simvastatin
Arm/Group Description	ezetimibe/simvastatin : ezetimibe/simvastatin 10/20 mg daily placebo for each medication	simvastatin: simvastatin 20 mg daily placebo for each medication
Period Title: Overall Study
STARTED	4	5
COMPLETED	4	5
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Vytorin	Zocor	Total
Arm/Group Description	simvastatin, ezetimibe/simvastatin : simvastatin 20 mg daiy ezetimibe/simvastatin 10/20 mg daily placebo for each medication	simvastatin, ezetimibe/simvastatin : simvastatin 20 mg daiy ezetimibe/simvastatin 10/20 mg daily placebo for each medication	Total of all reporting groups
Overall Participants	4	5	9
Age (Count of Participants)
<=18 years	4 100%	5 100%	9 100%
Between 18 and 65 years	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.7 (1.8)	17.5 (2.3)	15.8 (2.8)
Sex: Female, Male (Count of Participants)
Female	1 25%	3 60%	4 44.4%
Male	3 75%	2 40%	5 55.6%
Region of Enrollment (participants) [Number]
United States	4 100%	5 100%	9 100%

Outcome Measures

1. Primary Outcome

Title	Change in LDL-c From Baseline to 6 Months in Subjects With Type 1 Diabetes Taking Vytorin or Zocor.
Description	Change in LDL-c between Zocor and Vytorin treatment in subjects with Type 1 Diabetes measured at baseline to the 6-month study visit.
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

Recruitment for this study failed to meet target. Due to the small sample size the analyses of these data were primarily descriptive.

Arm/Group Title	Vytorin (Ezetimibe/Simvastatin)	Zocor (Simvastatin)
Arm/Group Description	ezetimibe/simvastatin : ezetimibe/simvastatin 10/20 mg daily placebo for each medication	simvastatin: simvastatin 20 mg daily placebo for each medication
Measure Participants	4	5
Mean (Standard Deviation) [mg/dl]	-67 (47)	-6 (25)

Adverse Events

Time Frame	All Serious Adverse Events (SAEs) will be reported to the Clinical Translational Research Center (CTRC), Data Safety Monitoring Board (DSMB), Research Subject Advocate (RSA) and the Colorado Multiple Institutional Review Board (COMIRB) within 5 days
Adverse Event Reporting Description	SAEs will also be reported to the FDA since this protocol is under an Investigational New Drug (IND). Adverse Events (AEs) will be batched and reported to the DSMB as part of the periodic reports and to COMIRB at the time of continuing review.
Arm/Group Title	Vytorin (Simvastatin + Ezetimibe)		Zocor [Simvastatin]
Arm/Group Description	Vytorin [simvastatin + ezetimibe]20 mg taken daily for 6 months to compare in a 2- arm design to Zocor [simvastatin] .		Zocor [simvastatin] 20 mg taken daily for 6 months to compare in a 2- arm design to Vytorin [simvastatin + ezetimibe].
All Cause Mortality
	Vytorin (Simvastatin + Ezetimibe)		Zocor [Simvastatin]
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Vytorin (Simvastatin + Ezetimibe)		Zocor [Simvastatin]
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/5 (0%)
Other (Not Including Serious) Adverse Events
	Vytorin (Simvastatin + Ezetimibe)		Zocor [Simvastatin]
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/4 (0%)		0/5 (0%)

Limitations/Caveats

Recruitment for this study failed to meet target and therefore it is difficult to make conclusions on the data obtained in these 9 subjects. No secondary outcomes were measured as recruitment was insufficient and study was stopped after only 9 subjects completed trial.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 30 days from the time submitted to the sponsor for review.