Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

RISE Pediatric Medication Study (RISE Peds)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01779375
Recruitment Status : Completed
First Posted : January 30, 2013
Results First Posted : October 9, 2018
Last Update Posted : December 10, 2019
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
RISE Study Group

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Prediabetes
Type 2 Diabetes
Interventions Drug: Metformin
Drug: Glargine
Enrollment 91
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Metformin Alone Glargine Followed by Metformin
Hide Arm/Group Description Metformin was titrated beginning at 500 mg/day to the maximum dose tolerated (up to 2000 mg/day). Basal insulin glargine was titrated to achieve a morning fasting blood glucose of 85-95 mg/dl and continued through 3 months after which metformin was titrated as in the Metformin alone arm and continued for 9 months.
Period Title: Overall Study
Started 47 44
Completed 45 41
Not Completed 2 3
Arm/Group Title Metformin Alone Glargine Followed by Metformin Total
Hide Arm/Group Description Metformin was titrated beginning at 500 mg/day to the maximum dose tolerated (up to 2000 mg/day). Basal insulin glargine was titrated to achieve a morning fasting blood glucose of 85-95 mg/dl and continued through 3 months after which metformin was titrated as in the Metformin alone arm and continued for 9 months. Total of all reporting groups
Overall Number of Baseline Participants 47 44 91
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 47 participants 44 participants 91 participants
<=18 years
47
 100.0%
42
  95.5%
89
  97.8%
Between 18 and 65 years
0
   0.0%
2
   4.5%
2
   2.2%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 47 participants 44 participants 91 participants
13.9  (2.1) 14.9  (2.0) 14.4  (2.1)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 47 participants 44 participants 91 participants
Female
38
  80.9%
27
  61.4%
65
  71.4%
Male
9
  19.1%
17
  38.6%
26
  28.6%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 47 participants 44 participants 91 participants
Non-hispanic white
12
  25.5%
13
  29.5%
25
  27.5%
Black
9
  19.1%
14
  31.8%
23
  25.3%
Hispanic
20
  42.6%
14
  31.8%
34
  37.4%
All othe
6
  12.8%
3
   6.8%
9
   9.9%
BMI  
Mean (Standard Deviation)
Unit of measure:  Kg/m^2
Number Analyzed 47 participants 44 participants 91 participants
36.9  (6.4) 36.5  (6.4) 36.7  (6.4)
HbA1c  
Mean (Standard Deviation)
Unit of measure:  % of glycosylated hemoglobin
Number Analyzed 47 participants 44 participants 91 participants
5.7  (0.6) 5.7  (0.6) 5.7  (0.6)
Fasting glucose  
Mean (Standard Deviation)
Unit of measure:  Mg/dl
Number Analyzed 47 participants 44 participants 91 participants
109.2  (19.7) 107.5  (14.1) 108.3  (17.1)
2-hour OGTT glucose  
Mean (Standard Deviation)
Unit of measure:  Mg/dl
Number Analyzed 47 participants 44 participants 91 participants
184.2  (50.2) 183.5  (44.5) 183.9  (47.3)
1.Primary Outcome
Title ß-cell Response Measured by Hyperglycemic Clamp
Hide Description Clamp measures of ß-cell response, co-primary outcomes
Time Frame 3-months after medication washout (Month 15)
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis was on all participants able to have a M15 visit. 2 participants in the metformin alone arm decompensated at M12 and were unable to remain off treatment until M15. A sensitivity analysis including these 2 participants using 1/2 of the worst value among all other participants did not alter the results.
Arm/Group Title Metformin Alone Glargine Followed by Metformin
Hide Arm/Group Description:
Metformin was titrated beginning at 500 mg/day to the maximum dose tolerated (up to 2000 mg/day).
Basal insulin glargine was titrated to achieve a morning fasting blood glucose of 85-95 mg/dl and continued through 3 months after which metformin was titrated as in the Metformin alone arm and continued for 9 months.
Overall Number of Participants Analyzed 43 41
Mean (95% Confidence Interval)
Unit of Measure: nmol/L
Steady State C-peptide
4.82
(2.07 to 11.23)
4.18
(1.74 to 10.08)
ACPRmax
6.92
(2.81 to 17.03)
5.95
(2.17 to 16.37)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin Alone, Glargine Followed by Metformin
Comments Seemingly unrelated regression was used to compare treatment arms on the combination of insulin sensitivity (M/I as calculated from the hyperglycemic clamp) and insulin secretion (steady-state C-peptide and ACPRmax as co-primary; ACPRg as major secondary,). See statistical analysis plan for further details and R code.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments All analyses were conducted with values on a log scale and re-exponentiated for presentation.
Method Regression, Linear
Comments Measures of ß-cell response were modeled simultaneously with insulin sensitivity (M/I) using 2-df seemingly unrelated regression models.
2.Primary Outcome
Title M/I
Hide Description Clamp measure of insulin sensitivity
Time Frame 3-months after a medication washout
Hide Outcome Measure Data
Hide Analysis Population Description
All participants with a Month 15 visit
Arm/Group Title Metformin Alone Glargine Followed by Metformin
Hide Arm/Group Description:

Metformin will be titrated to the maximum dose tolerated (up to 2000 mg/day).

Metformin

Basal insulin glargine for 3 months titrated to achieve a morning fasting blood glucose of 85-95 mg/dl, followed by metformin (titrated up to 2000 mg/day) for 9 months.

Metformin

Glargine

Overall Number of Participants Analyzed 43 41
Mean (95% Confidence Interval)
Unit of Measure: x 10-5 mmol/kg/min per pmol/L
1.48
(0.29 to 7.63)
1.70
(0.25 to 11.54)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin Alone, Glargine Followed by Metformin
Comments Analyses were completed on a log scale and re-exponentiated for presentation.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
3.Secondary Outcome
Title ACPRg
Hide Description First phase response
Time Frame 3-months after a medication washout
Hide Outcome Measure Data
Hide Analysis Population Description
Primary analysis was on all participants able to have a M15 visit.
Arm/Group Title Metformin Alone Glargine Followed by Metformin
Hide Arm/Group Description:

Metformin will be titrated to the maximum dose tolerated (up to 2000 mg/day).

Metformin

Basal insulin glargine for 3 months titrated to achieve a morning fasting blood glucose of 85-95 mg/dl, followed by metformin (titrated up to 2000 mg/day) for 9 months.

Metformin

Glargine

Overall Number of Participants Analyzed 43 41
Mean (95% Confidence Interval)
Unit of Measure: nmol/L
1.11
(0.14 to 8.56)
1.12
(0.15 to 8.35)
4.Secondary Outcome
Title ß-cell Function Measured by Hyperglycemic Clamp Techniques at M12
Hide Description Participants had 12-months of active therapy. Secondary results at the end of active intervention.
Time Frame End of active intervention (Month 12).
Hide Outcome Measure Data
Hide Analysis Population Description
Secondary analysis was on all participants with a Month 12 visit.
Arm/Group Title Metformin Alone Glargine Followed by Metformin
Hide Arm/Group Description:
Metformin was titrated beginning at 500 mg/day to the maximum dose tolerated (up to 2000 mg/day).
Basal insulin glargine was titrated to achieve a morning fasting blood glucose of 85-95 mg/dl and continued through 3 months after which metformin was titrated as in the Metformin alone arm and continued for 9 months.
Overall Number of Participants Analyzed 45 41
Mean (95% Confidence Interval)
Unit of Measure: nmol/L
Steady State C-peptide
4.78
(2.09 to 10.94)
4.37
(1.75 to 10.94)
ACPRmax
6.95
(3.16 to 15.28)
5.79
(2.49 to 13.46)
ACPRg
1.06
(0.10 to 11.33)
1.03
(0.05 to 21.73)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Metformin Alone, Glargine Followed by Metformin
Comments Analyses were completed on a log scale and re-exponentiated for display.
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value >0.05
Comments [Not Specified]
Method Regression, Linear
Comments [Not Specified]
5.Secondary Outcome
Title Clamp Measure of Insulin Sensitivity
Hide Description Participants had 12-months of active therapy. Secondary results at the end of active intervention.
Time Frame End of active intervention (Month 12)
Hide Outcome Measure Data
Hide Analysis Population Description
Secondary analysis was on all participants with a Month 12 visit.
Arm/Group Title Metformin Alone Glargine Followed by Metformin
Hide Arm/Group Description:

Metformin will be titrated to the maximum dose tolerated (up to 2000 mg/day).

Metformin

Basal insulin glargine for 3 months titrated to achieve a morning fasting blood glucose of 85-95 mg/dl, followed by metformin (titrated up to 2000 mg/day) for 9 months.

Metformin

Glargine

Overall Number of Participants Analyzed 45 41
Mean (95% Confidence Interval)
Unit of Measure: x 10-5 mmol/kg/min per pmol/L
1.52
(0.17 to 13.48)
1.93
(0.30 to 12.50)
6.Other Pre-specified Outcome
Title OGTT Measures of ß-cell Function and Glucose Tolerance
Hide Description Measures derived the OGTT at the end of the 12 month active intervention period, and following a 3-month and 9-month washout.
Time Frame After 12 months of active treatment, and 3 and 9 months of washout
Outcome Measure Data Not Reported
Time Frame Throughout the 21 month study period
Adverse Event Reporting Description AEs were captured at quarterly clinical visits and SAEs were captured as they occur or when reported at a subsequent clinical visit
 
Arm/Group Title Metformin Alone Glargine Followed by Metformin
Hide Arm/Group Description Metformin was titrated beginning at 500 mg/day to the maximum dose tolerated (up to 2000 mg/day). Basal insulin glargine was titrated to achieve a morning fasting blood glucose of 85-95 mg/dl and continued through 3 months after which metformin was titrated as in the Metformin alone arm and continued for 9 months.
All-Cause Mortality
Metformin Alone Glargine Followed by Metformin
Affected / at Risk (%) Affected / at Risk (%)
Total   0/47 (0.00%)      0/44 (0.00%)    
Hide Serious Adverse Events
Metformin Alone Glargine Followed by Metformin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/47 (10.64%)      2/44 (4.55%)    
Ear and labyrinth disorders     
Otitis externa   1/47 (2.13%)  1 0/44 (0.00%)  0
Tonsillectomy & Adenoidectomy   2/47 (4.26%)  2 0/44 (0.00%)  0
General disorders     
Appendicitis   0/47 (0.00%)  0 1/44 (2.27%)  1
Infections and infestations     
Pnemonia   1/47 (2.13%)  1 0/44 (0.00%)  0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Cancer  [1]  0/47 (0.00%)  0 1/44 (2.27%)  1
Psychiatric disorders     
Mental health hospitalization  [2]  1/47 (2.13%)  1 0/44 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
Ewing's Sarcoma
[2]
Suicide ideation
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Metformin Alone Glargine Followed by Metformin
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   30/47 (63.83%)      30/44 (68.18%)    
Endocrine disorders     
Low blood sugar  [1]  0/47 (0.00%)  16/44 (36.36%) 
Polyuria or polydipsia   11/47 (23.40%)  11/44 (25.00%) 
Gastrointestinal disorders     
GI Discomfort   16/47 (34.04%)  17/44 (38.64%) 
Skin and subcutaneous tissue disorders     
Skin rash   6/47 (12.77%)  6/44 (13.64%) 
Indicates events were collected by systematic assessment
[1]
self monitored blood glucose <70 mg/dl during 3 months of glargine treatment
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
Layout table for Results Point of Contact information
Name/Title: Sharon Edelstein
Organization: George Washington University Biostatistics Center
Phone: 3018819260
EMail: sharone@bsc.gwu.edu
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: RISE Study Group
ClinicalTrials.gov Identifier: NCT01779375    
Other Study ID Numbers: RISE Pediatric
5U01DK094406-02 ( U.S. NIH Grant/Contract )
First Submitted: January 28, 2013
First Posted: January 30, 2013
Results First Submitted: August 30, 2018
Results First Posted: October 9, 2018
Last Update Posted: December 10, 2019