Trial Outcomes & Findings for Statins in Children With Type 1 Diabetes and Hypercholesterolemia (NCT NCT01236365)

Last Updated: 2019-06-25

Results Overview

To assess if the use of statins in children with type 1 DM is safe, improves measures of LDL-C. Subjects will have a physical exam, laboratories, nutritional counseling and moderate aerobic exercise recommended. Diabetes management will be intensified. At 3 months fasting lipoprotein fractions (ion mobility)re-drawn and if LDL-C \>100mg/dl patients will be randomized to treatment with statins or placebo for 6 months, randomization stratified by BP and microalbuminuria, duration of diabetes and HgA1C. At 1 month safety labs will be repeated and blood withdrawn again at 3 and 6 months from baseline.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

42 participants

Primary outcome timeframe

Randomization and 6 months

Results posted on

2019-06-25

Participant Flow

Participant milestones

Participant milestones
Measure	Atorvastatin Atorvastatin: 10 or 20 mg daily	Placebo Placebo: 10 or 20 mg daily
Overall Study STARTED	21	21
Overall Study COMPLETED	19	19
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Atorvastatin Atorvastatin: 10 or 20 mg daily	Placebo Placebo: 10 or 20 mg daily
Overall Study Lost to Follow-up	0	2
Overall Study Moved Out of State	1	0
Overall Study Dropped at Randomization due to high LFT	1	0

Baseline Characteristics

Statins in Children With Type 1 Diabetes and Hypercholesterolemia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Atorvastatin n=21 Participants Atorvastatin: 10 or 20 mg daily	Placebo n=21 Participants Atorvastatin Placebo: 10 or 20 mg daily	Total n=42 Participants Total of all reporting groups
Age, Continuous	14.9 years STANDARD_DEVIATION 2.2 • n=5 Participants	15.4 years STANDARD_DEVIATION 2.7 • n=7 Participants	15.1 years STANDARD_DEVIATION 2.4 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants	9 Participants n=7 Participants	20 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants	12 Participants n=7 Participants	22 Participants n=5 Participants
Race/Ethnicity, Customized non-Hispanic white	17 participants n=5 Participants	14 participants n=7 Participants	31 participants n=5 Participants
Race/Ethnicity, Customized Other	4 participants n=5 Participants	7 participants n=7 Participants	11 participants n=5 Participants
Region of Enrollment United States	21 participants n=5 Participants	21 participants n=7 Participants	42 participants n=5 Participants

PRIMARY outcome

Timeframe: Randomization and 6 months

Population: Project #1. Adjusted for age, gender and ISS (Insulin sensitivity score)

Outcome measures

Outcome measures
Measure	Atorvastatin LDL-C at Randomization n=19 Participants	Atorvastatin LDL-C at 6 Months n=19 Participants	Placebo LDL-C at Randomization n=19 Participants	Placebo LDL-C at 6 Months n=19 Participants
LDL-C Levels Assessed at Randomization and 6 Months	128 mg/dL Standard Error 4	87 mg/dL Standard Error 5	126 mg/dL Standard Error 5	133 mg/dL Standard Error 8

PRIMARY outcome

Timeframe: Randomization and 6 months

Population: Project #1

To assess if the use of statins in children with type 1 DM decreases the concentration of inflammatory markers.

Outcome measures

Outcome measures
Measure	Atorvastatin LDL-C at Randomization n=19 Participants	Atorvastatin LDL-C at 6 Months n=19 Participants	Placebo LDL-C at Randomization n=19 Participants	Placebo LDL-C at 6 Months n=19 Participants
Hs-CRP Levels Assessed at Randomization and 6 Months	0.363 mg/dL Interval 0.148 to 0.817	0.419 mg/dL Interval 0.165 to 1.092	0.248 mg/dL Interval 0.149 to 0.959	0.446 mg/dL Interval 0.181 to 0.958

SECONDARY outcome

Timeframe: Randomization and 6 months

Population: Project #1. 4 Atorvastatin and 8 Placebo Subjects did not complete their CGM at 6months.

Mean amplitude of glycemic excursion (MAGE) with continuous glucose monitoring (CGM - IPro®, Medtronic Minimed) worn blindly for 6d to assess glucose variability

Outcome measures

Outcome measures
Measure	Atorvastatin LDL-C at Randomization n=19 Participants	Atorvastatin LDL-C at 6 Months n=15 Participants	Placebo LDL-C at Randomization n=19 Participants	Placebo LDL-C at 6 Months n=11 Participants
MAGE	150 mg/dL Standard Error 9	156 mg/dL Standard Error 13	156 mg/dL Standard Error 6	152 mg/dL Standard Error 8

SECONDARY outcome

Timeframe: Randomization and 6 months

Population: Project #2. Study Subjects were given the option to participate in the Project #2 genetic substudy; 9 Atorvastatin and 12 Placebo Subjects participated in Project #2. 1 Atorvastatin and 1 Placebo Subject did not complete the 6 month genetic test.

Receptor for Advanced Glycation End Products

Outcome measures

Outcome measures
Measure	Atorvastatin LDL-C at Randomization n=9 Participants	Atorvastatin LDL-C at 6 Months n=8 Participants	Placebo LDL-C at Randomization n=12 Participants	Placebo LDL-C at 6 Months n=11 Participants
RAGE	49 pg/mL Standard Error 11	35 pg/mL Standard Error 5	50 pg/mL Standard Error 7	58 pg/mL Standard Error 17

SECONDARY outcome

Timeframe: Randomization

Population: Project #3. Study Subjects were given the option to participate in the Project #3 MRI substudy; 11 Atorvastatin and 8 Placebo Subjects participated in Project #3.

Subclinical atherosclerosis and arterial stiffness of abdominal aortic MRI

Outcome measures

Outcome measures
Measure	Atorvastatin LDL-C at Randomization n=11 Participants	Atorvastatin LDL-C at 6 Months n=8 Participants	Placebo LDL-C at Randomization	Placebo LDL-C at 6 Months
Descending Aortic Strain	27.2 percent area change Standard Deviation 6.4	29 percent area change Standard Deviation 8.5	—	—

Adverse Events

Atorvastatin

Serious events: 1 serious events

Other events: 11 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 7 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Atorvastatin n=21 participants at risk Atorvastatin: 10 or 20 mg daily	Placebo n=21 participants at risk Atorvastatin Placebo: 10 or 20 mg daily
Musculoskeletal and connective tissue disorders Fall	4.8% 1/21 • Number of events 1	0.00% 0/21

Other adverse events

Other adverse events
Measure	Atorvastatin n=21 participants at risk Atorvastatin: 10 or 20 mg daily	Placebo n=21 participants at risk Atorvastatin Placebo: 10 or 20 mg daily
Skin and subcutaneous tissue disorders Cut/Laceration	4.8% 1/21 • Number of events 1	9.5% 2/21 • Number of events 2
Skin and subcutaneous tissue disorders Rash	9.5% 2/21 • Number of events 2	4.8% 1/21 • Number of events 1
Skin and subcutaneous tissue disorders Acne	4.8% 1/21 • Number of events 1	0.00% 0/21
Musculoskeletal and connective tissue disorders Costochondritis	4.8% 1/21 • Number of events 1	4.8% 1/21 • Number of events 2
Gastrointestinal disorders Stomach Discomfort	9.5% 2/21 • Number of events 2	14.3% 3/21 • Number of events 3
Gastrointestinal disorders Acid Reflux	4.8% 1/21 • Number of events 1	4.8% 1/21 • Number of events 1
Reproductive system and breast disorders Ovarian Cyst	0.00% 0/21	4.8% 1/21 • Number of events 1
Renal and urinary disorders Hematuria with Flank Pain	4.8% 1/21 • Number of events 2	0.00% 0/21
Nervous system disorders Headache	0.00% 0/21	4.8% 1/21 • Number of events 1
Musculoskeletal and connective tissue disorders Lower Extremity Cramping	9.5% 2/21 • Number of events 2	9.5% 2/21 • Number of events 2
Musculoskeletal and connective tissue disorders Hand Fracture	0.00% 0/21	4.8% 1/21 • Number of events 1
Ear and labyrinth disorders Sinus Symptoms	9.5% 2/21 • Number of events 2	9.5% 2/21 • Number of events 2
Infections and infestations Throat Infection	9.5% 2/21 • Number of events 2	4.8% 1/21 • Number of events 3
Hepatobiliary disorders Abnormal Chemistry Labs	4.8% 1/21 • Number of events 1	4.8% 1/21 • Number of events 2
Musculoskeletal and connective tissue disorders Elevated CK Blood Level	4.8% 1/21 • Number of events 2	0.00% 0/21
Nervous system disorders Hypoglycemic Seizure	4.8% 1/21 • Number of events 1	0.00% 0/21
Social circumstances Fatigue	9.5% 2/21 • Number of events 2	0.00% 0/21

Additional Information

Nelly Mauras, MD

Nemours Children's Clinic

Phone: 904-697-3674

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place