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Atorvastatin in New Onset Type 1 Diabetes Mellitus (T1DM) (TIDM)

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ClinicalTrials.gov Identifier: NCT00529191
Recruitment Status : Completed
First Posted : September 14, 2007
Results First Posted : March 8, 2013
Last Update Posted : March 13, 2017
Sponsor:
Collaborators:
FDA Office of Orphan Products Development
Medical University of South Carolina
Information provided by (Responsible Party):
Children's Hospital of Philadelphia

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Investigator);   Primary Purpose: Treatment
Condition Type 1 Diabetes
Interventions Drug: Atorvastatin
Other: Placebo
Enrollment 40
Recruitment Details Patients were recruited from medical clinics at CHOP from July 2007- January 2010
Pre-assignment Details  
Arm/Group Title Atorvastatin Placebo
Hide Arm/Group Description Two out of every 3 patients will receive atorvastatin in tablet form. The subject will start on 10mg of atorvastatin daily for four weeks, and then titrate up to 20mg daily. There will be 12 months of treatment followed by 6 months of a washout period. Placebo treated. Patients will receive tablets daily.There will be 12 months of treatment followed by 6 months of a washout period.
Period Title: Overall Study
Started 27 13
Completed 24 13
Not Completed 3 0
Arm/Group Title Atorvastatin Placebo Total
Hide Arm/Group Description Two out of every 3 patients will receive atorvastatin. Placebo treatment Total of all reporting groups
Overall Number of Baseline Participants 27 13 40
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 13 participants 40 participants
<=18 years
26
  96.3%
12
  92.3%
38
  95.0%
Between 18 and 65 years
1
   3.7%
1
   7.7%
2
   5.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 27 participants 13 participants 40 participants
13.38  (1.96) 13.30  (2.03) 13.33  (2.055)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 27 participants 13 participants 40 participants
Female
11
  40.7%
9
  69.2%
20
  50.0%
Male
16
  59.3%
4
  30.8%
20
  50.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 27 participants 13 participants 40 participants
27 13 40
1.Primary Outcome
Title Efficacy of a Daily Dose of Atorvastatin to Maintain Islet Cell Function as Measured by a 4-hour C-peptide Area Under Curve (AUC) in Patients With Newly Diagnosed Type 1 Diabetes Mellitus
Hide Description The change in C-peptide measurements collected over a 4 hour period (0, 30, 60, 90, 120, 150, 180, 210 and 240 minutes) after a Mixed Meal Tolerance Test at baseline vs 12 months post-treatment were calculated. The area under the curve for these combined measurements is calculated and the unit of measure is nanogram x minutes / mL. Efficacy (success) is defined by < 7.5% reduction in AUC for 4-hr MMTT.
Time Frame Baseline vs 12-month
Hide Outcome Measure Data
Hide Analysis Population Description
Participants who completed their 12-month treatment were included in the analysis, in which the change in C-peptide AUC at baseline and 12-months were calculated. Efficacy (success) is defined by < 7.5% reduction in AUC for 4-hr MMTT.
Arm/Group Title Atorvastatin Placebo
Hide Arm/Group Description:
Two out of every 3 patients will receive atorvastatin.
Placebo treatment
Overall Number of Participants Analyzed 27 13
Mean (Standard Deviation)
Unit of Measure: nanogram*minutes/ml
345  (679) 178  (308)
2.Secondary Outcome
Title % Subjects Without Change in 2-hour C-peptide AUC in Response to the MMTT at Baseline vs. 12 Months
Hide Description The C-peptide AUC measurements are collected over a 2 hour period (with 30 minute intervals) after a Mixed Meal Tolerance Test. The area under the curve from these combined measurements (from 0 to 120 or 0 to 240 minutes) is calculated and the unit of measure is nanogram*minutes/ml. The change in C-peptide AUC in response to a 2 hour MMTT at baseline vs 12 months were calculated, and efficacy (success) is defined as < 7.5% reduction.
Time Frame Baseline vs 12 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Atorvastatin Placebo
Hide Arm/Group Description:
Two out of every 3 patients will receive atorvastatin.
Placebo treatment
Overall Number of Participants Analyzed 27 13
Measure Type: Number
Unit of Measure: % of participants with efficacy
14.8 38.4
3.Secondary Outcome
Title Mean Daily Insulin Dose Per kg Body Weight for 7 Days
Hide Description Mean daily insulin dose per kg body weight for the 1 week preceding each scheduled study visit.
Time Frame Visit 1, 2, 3, 4, 5, 6, 7
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Atorvastatin Placebo
Hide Arm/Group Description:

Two out of every three patients will receive atorvastatin.

Atorvastatin: Pill, initially at 10 mg, then after 4 weeks, 20 mg Once daily for a total of 12 months

Placebo treated. Patients will receive tablets daily.There will be 12 months of treatment followed by 6 months of a washout period.
Overall Number of Participants Analyzed 27 13
Mean (Standard Deviation)
Unit of Measure: units/kg
Visit 1 0.53  (0.26) 0.62  (0.26)
Visit 2 0.50  (0.25) 0.52  (0.22)
Visit 3 0.48  (0.21) 0.50  (0.26)
Visit 4 0.59  (0.21) 0.47  (0.30)
Visit 5 0.64  (0.22) 0.59  (0.35)
Visit 6 0.65  (0.24) 0.64  (0.36)
Visit 7 0.70  (0.35) 0.71  (0.34)
4.Secondary Outcome
Title Levels of HbA1c at Months 3, 6, 9, 12 and 18
Hide Description [Not Specified]
Time Frame 3, 6, 9, 12, and 18 months
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Atorvastatin Placebo
Hide Arm/Group Description:

Two out of every three patients will receive atorvastatin.

Atorvastatin: Pill, initially at 10 mg, then after 4 weeks, 20 mg Once daily for a total of 12 months

One out of three subjects will receive a placebo.

Placebo: One out of three subjects will receive a placebo.

Overall Number of Participants Analyzed 27 13
Mean (Standard Deviation)
Unit of Measure: percentage of glycated hemoglobin
3 months 6.68  (0.95) 6.39  (0.95)
6 months 7.13  (0.90) 6.62  (1.22)
9 months 7.47  (1.44) 6.86  (0.91)
12 months 7.38  (1.19) 7.26  (1.45)
18 months 8.04  (1.82) 7.94  (2.62)
5.Secondary Outcome
Title Blood Glucose Control (Number of Participants With Hypoglycemia)
Hide Description Blood glucose control as determined from home glucose meter downloads for the 1 week preceding the visit. The number of subjects with hypoglycemic episodes requiring treatment (BG < 70 mg/dl)
Time Frame Baseline, Month 12, Month 18
Hide Outcome Measure Data
Hide Analysis Population Description
All participants contributing data
Arm/Group Title Atorvastatin Placebo
Hide Arm/Group Description:

Participants in Atorvastatin arm who had hypoglycemic episodes requiring treatment

Two out of every three patients will receive atorvastatin.

Atorvastatin: Pill, initially at 10 mg, then after 4 weeks, 20 mg Once daily for a total of 12 months

Participants in placebo arm who had hypoglycemic episodes requiring treatment

Placebo treated. Patients will receive tablets daily.There will be 12 months of treatment followed by 6 months of a washout period.

Overall Number of Participants Analyzed 27 13
Measure Type: Count of Participants
Unit of Measure: Participants
Baseline
16
  59.3%
7
  53.8%
12 Month
16
  59.3%
9
  69.2%
18 Month
8
  29.6%
8
  61.5%
6.Secondary Outcome
Title Number of Episodes of Hypoglycemia Requiring Any Treatment
Hide Description number of episodes of hypoglycemia requiring any treatment, defined by the need for treatment with glucagon or third party intervention.
Time Frame Baseline, Month 12, Month 18
Hide Outcome Measure Data
Hide Analysis Population Description
All subjects contributing data
Arm/Group Title Atorvastatin Placebo
Hide Arm/Group Description:

Participants in Atorvastatin arm who had hypoglycemic episodes requiring treatment

Two out of every three patients will receive atorvastatin.

Atorvastatin: Pill, initially at 10 mg, then after 4 weeks, 20 mg Once daily for a total of 12 months

Participants in placebo arm who had hypoglycemic episodes requiring treatment

Placebo treated. Patients will receive tablets daily.There will be 12 months of treatment followed by 6 months of a washout period.

Overall Number of Participants Analyzed 27 13
Mean (Standard Deviation)
Unit of Measure: episodes
Baseline Number Analyzed 16 participants 7 participants
4.13  (3.95) 2.86  (3.98)
Month 12 Number Analyzed 16 participants 9 participants
3.44  (3.01) 2.44  (2.51)
Month 18 Number Analyzed 8 participants 8 participants
2.75  (3.65) 2.5  (2.2)
7.Secondary Outcome
Title Study Drug Compliance Rate Overall
Hide Description Compliance is defined as >=80% expected dosage consumed during the visit period.
Time Frame 12 months treatment
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Atorvastatin Placebo
Hide Arm/Group Description:

Two out of every three patients will receive atorvastatin.

Atorvastatin: Pill, initially at 10 mg, then after 4 weeks, 20 mg Once daily for a total of 12 months

Placebo treated. Patients will receive tablets daily.There will be 12 months of treatment followed by 6 months of a washout period.
Overall Number of Participants Analyzed 27 13
Measure Type: Number
Unit of Measure: % of compliant participants
85.1 76.9
8.Secondary Outcome
Title HDL and LDL Cholesterol Levels in Participants Stratified by the Preservation of Islet Cell Function
Hide Description

Relationship between atorvastatin's effect on HDL and LDL cholesterol and the preservation of islet cell function.

Islet cell preservation defined as: <7.5% Reduction in C-Pep

Time Frame Baseline, Week 1, Month 3, Month 6, Month 9, Month 12,
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Atorvastatin NO Islet Cell Preservation Placebo NO Islet Cell Preservation Atorvastatin YES Islet Cell Preservation Placebo YES Islet Cell Preservation
Hide Arm/Group Description:

Two out of every three patients will receive atorvastatin.

Atorvastatin: Pill, initially at 10 mg, then after 4 weeks, 20 mg Once daily for a total of 12 months

Placebo treated. Patients will receive tablets daily.There will be 12 months of treatment followed by 6 months of a washout period.

Two out of every three patients will receive atorvastatin.

Atorvastatin: Pill, initially at 10 mg, then after 4 weeks, 20 mg Once daily for a total of 12 months

Placebo treated. Patients will receive tablets daily.There will be 12 months of treatment followed by 6 months of a washout period.
Overall Number of Participants Analyzed 24 8 3 5
Mean (Standard Deviation)
Unit of Measure: mg/dl
Baseline- HDL Cholesterol (mg/dL) 47.58  (16.39) 44.75  (18) 47.33  (2.31) 53.2  (16.39)
Baseline - LDL Cholesterol (mg/dL) 99.04  (22.37) 96.13  (22.99) 83.67  (25.97) 99  (13.04)
Week 1- HDL Cholesterol (mg/dL) 45.43  (14.33) 48.25  (14.26) 52.33  (5.69) 47.2  (13.88)
Week 1 - LDL Cholesterol (mg/dL) 68.91  (16.4) 97.63  (17.9) 57.67  (12.06) 86.4  (12.46)
Month 3- HDL Cholesterol (mg/dL) 45.05  (14.49) 48.25  (18.69) 43.33  (4.04) 49.25  (12.31)
Month 3 - LDL Cholesterol (mg/dL) 61  (20.88) 106.25  (18.44) 48  (12.17) 91.5  (20.21)
Month 6- HDL Cholesterol (mg/dL) 48  (16.07) 50.5  (20.7) 51.67  (5.51) 54.75  (19.47)
Month 6 - LDL Cholesterol (mg/dL) 63.1  (24.52) 102.5  (16.21) 54  (7) 96.75  (20.93)
Month 9- HDL Cholesterol (mg/dL) 49.1  (14.86) 45.88  (12.57) 55.33  (11.15) 50  (21.71)
Month 9 - LDL Cholesterol (mg/dL) 67.24  (24.7) 97  (4.17) 65.33  (28.01) 90.75  (8.06)
Month 12 - HDL Cholesterol (mg/dL) 47.95  (14.49) 45.75  (16.34) 57.33  (14.15) 47  (8.31)
Month 12 - LDL Cholesterol (mg/dL) 61.52  (20.04) 102.75  (20.9) 66  (23.64) 96.4  (6.66)
Time Frame Events were reported over the one year treatment phase of the study.
Adverse Event Reporting Description Adverse events were reported or observed at interim visits, and were systematically collected.
 
Arm/Group Title Atorvastatin Placebo
Hide Arm/Group Description Two out of every 3 patients will receive atorvastatin. Placebo treatment
All-Cause Mortality
Atorvastatin Placebo
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Atorvastatin Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/27 (0.00%)      0/13 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Atorvastatin Placebo
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   23/27 (85.19%)      10/13 (76.92%)    
Endocrine disorders     
Hypoglycemia   3/27 (11.11%)  3 0/13 (0.00%)  0
Gastrointestinal disorders     
Nausea  [1]  4/27 (14.81%)  5 2/13 (15.38%)  2
Gastroenteritis  [1]  4/27 (14.81%)  4 2/13 (15.38%)  2
Diarrhea  [1]  1/27 (3.70%)  1 2/13 (15.38%)  2
General disorders     
Fever  [1]  8/27 (29.63%)  11 2/13 (15.38%)  2
Nervous system disorders     
Headache  [2]  7/27 (25.93%)  11 3/13 (23.08%)  3
Respiratory, thoracic and mediastinal disorders     
Nasal Congestion  [1]  1/27 (3.70%)  1 2/13 (15.38%)  4
Respiratory Infection  [3]  9/27 (33.33%)  11 4/13 (30.77%)  7
Sore Throat  [1]  3/27 (11.11%)  3 1/13 (7.69%)  2
Indicates events were collected by systematic assessment
[1]
Reported or observed at interim visit.
[2]
Patient report of headache at interim assessment.
[3]
Respiratory Infection reported or observed at interim visit.
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Steven Willi, MD
Organization: Children's Hospital of Philadelphia
Phone: 215-590-3174
EMail: willi@chop.email.edu
Layout table for additonal information
Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT00529191     History of Changes
Other Study ID Numbers: 2006-5-4824
R01FD003340 ( U.S. FDA Grant/Contract )
First Submitted: September 13, 2007
First Posted: September 14, 2007
Results First Submitted: December 20, 2012
Results First Posted: March 8, 2013
Last Update Posted: March 13, 2017