Comparison of Glycemic Control in Obese Diabetics Using Three Different Pen Needles

Study Overview
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Brief Summary
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Anxiety about needles is a concern commonly expressed by diabetics when beginning insulin therapy. A shorter, thinner pen needle that delivers insulin with the safety and efficacy profile of longer pen needles may appeal to many diabetic patients as the shorter needle may be perceived as less intimidating and more comfortable. While pen needles of 4 to 8 mm in length are generally used for insulin injection in patients considered thin or normal weight, longer (12.7 mm) needles are still often prescribed for overweight or obese patients with diabetes. Since skin thickness is nearly constant across a range of body mass index (BMI), a clear rationale exists for the use of shorter needles in obese patients. (Gibney et al., CMRO 2010) The primary purpose of this study is to evaluate whether the BD Ultra-Fine™ Nano 4mm x 32 Gauge(G) pen needle manufactured by Becton, Dickinson and Company (BD) provides equivalent glucose control (as measured by hemoglobin A1c levels) as the BD Ultra-Fine™ 8mm x 31G and the BD Ultra-Fine™ 12.7mm x 29G pen needles in obese subjects with diabetes.

Detailed Description
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Each subject's participation is expected to last a total of 7 months and includes a screening visit, a three-week wash-in period (one week with each of the three different size pen needles) followed by two consecutive 12 week study periods. The purpose of the three week wash-in period is to minimize the number of dropouts during the following study periods by ensuring that subjects have experience using each of the three study needles and find them generally acceptable for use during the study. Only subjects who complete the wash-in period and confirm their agreement to continue participating will be randomized into one of the two study arms. Subjects will be randomly assigned to use the BD Ultra-Fine™ 4mm pen needle and either the BD Ultra-Fine™ 8mm pen needle or the BD Ultra-Fine™ 12.7mm pen needle. The randomization will also specify which of the two study pen needles to be used first. Half of the study subjects will use the BD Ultra-Fine™ 4mm and BD Ultra-Fine™ 8mm pen needles (4mm/8mm arm) and the other half will use the BD Ultra-Fine™ 4mm and the BD Ultra-Fine™ 12.7mm pen needles (4mm/12.7mm arm). At the end of the first 12 week study period subjects will switch to the other assigned pen needle for the second and final study period. Glycemic control (based on HbA1c concentrations) will be assessed at baseline and at the end of each 12 week study period.

Official Title
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Comparison of Glycemic Control in Obese Subjects With Diabetes Using the BD Ultra-Fine™ Nano 4mm x 32G Pen Needle, and Either the BD Ultra-Fine™ Short 8mm x 31G Pen Needle or the BD Ultra Fine™ 12.7mm x 29G Pen Needle

Conditions
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Diabetes Mellitus, Type 1, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Device: 4 mm x 32G Pen Needle
* Device: 8mm x 31G Pen Needle
* Device: 12.7mm x 29G Pen Needle


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Insulin requiring diabetics (type 1 or type 2) Using a pen device for self-injection of all diabetes-related medications for at least two months prior to screening. 18 to 80 years of age, inclusive. Body Mass Index of at least 30 kg/m². Hemoglobin A1c from 5.5 to 9.5 percent (%), inclusive. Self-monitor blood glucose at least twice per day with a memory blood glucose meter, and willing to do so at least twice per day for the duration of the study On a stable diabetes treatment regimen (for example, no change to non-insulin therapies)for at least 2 months prior to screening Able to read, write and follow instructions in English or Spanish. Exclusion Criteria: Administer insulin with a pump. Currently use a syringe to inject insulin or any other diabetes-related medication. Pregnancy. History of intravenous drug abuse. Current status or history of a medical condition that would contraindicate treatment with the study product or other conditions which, in the opinion of the Investigator, would place the subject at risk or have the potential to confound interpretation of the study results (i.e. recent history of ketoacidosis, hypoglycemic unawareness, etc.) Participated in any one of the following clinical studies: BDDC-08-011, 'Comparison of Glycemic Control among Diabetics using the 4mm x 32G BD Pen Needle versus the 8mm x 31G BD Pen Needle and the 5mm x 31G BD Pen Needle'. DBC-10-SQUIR04, 'Evaluation of Glycemic Control and User Acceptability of the BD Ultrafine Nano 4mm x 32G Pen Needle for Injection of Long-Acting or Basal Insulin Doses Above 40 Units' DBC-10-EMRLD01, 'Design Validation of BD 5-bevel Pen Needles (4,5 and 8mm) in Subjects with Diabetes'

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 4 mm vs. 8 mm<br>Subjects randomized to this study arm first used either the 4 mm x 32G Pen Needle or the 8mm x 31G Pen Needle for 12 weeks (Period 1), then switched to the alternate pen needle (PN) for another 12 weeks (Period 2). Order of PN use was randomly determined. | Device: 4 mm x 32G Pen Needle<br>* During the 12 week study period, subjects use this pen needle with their own pen device for all daily insulin injections they usually administered themselves with a pen device. Subjects follow their usual insulin regimen and there is no upper limit on total daily insulin dosage or number of injections. Subjects are advised to inject straight in when using the 4mm PN, with no pinch up.<br>* Other names: BD Ultra-Fine™ Nano pen needle, Catalog number 320122;Device: 8mm x 31G Pen Needle<br>* During the 12 week study period, subjects will use this pen needle with their own pen device for all daily insulin injections they usually administered themselves with a pen device. Subjects follow their usual insulin regimen and there is no upper limit on total daily insulin dosage or number of injections. Subjects are directed to use pinch-up when injecting in the abdomen or thigh with the 8mm PN, and no pinch-up at other injection sites.<br>* Other names: BD Ultra-Fine™ Short pen needle, Catalog number 320109;|
| Experimental: 4 mm vs. 12.7 mm<br>Subjects randomized to this study arm first used either the 4 mm x 32G Pen Needle or the 12.7mm x 29G Pen Needle (PN) for 12 weeks (Period 1), then switched to the alternate PN for another 12 weeks (Period 2). Order of PN use was randomly determined. | Device: 4 mm x 32G Pen Needle<br>* During the 12 week study period, subjects use this pen needle with their own pen device for all daily insulin injections they usually administered themselves with a pen device. Subjects follow their usual insulin regimen and there is no upper limit on total daily insulin dosage or number of injections. Subjects are advised to inject straight in when using the 4mm PN, with no pinch up.<br>* Other names: BD Ultra-Fine™ Nano pen needle, Catalog number 320122;Device: 12.7mm x 29G Pen Needle<br>* During the 12 week study period, subjects will use this pen needle with their own pen device for all daily insulin injections they usually administered themselves with a pen device. Subjects follow their usual insulin regimen and there is no upper limit on total daily insulin dosage or number of injections. When using the 12.7mm PN, subjects are instructed to insert either at an angle of 45 degrees, or to pinch up and hold the pen device at a 90 degree angle (straight in).<br>* Other names: BD Ultra-Fine™ Original pen needle, BD Catalog Number 328203;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic Control as Measured by HbA1c (4 mm vs. 8 mm) | Subjects' glycemic control was assessed by comparing hemoglobin A1c (HbA1c) levels measured at the end of each 12 week Study Period (e.g., at Visit 5 or Visit 7) to the HbA1c measured at the start of that Study Period, i.e. the baseline (Visit 3) for Period 1 and the Period 1/2 crossover (Visit 5) for Period 2. Analysis included only subjects with HbA1C values at baseline (Visit 3) and at the end of Study Period 1 (Visit 5) and end of Period 2 (Visit 7). | Over each 12 week study period | 
| Glycemic Control as Measured by HbA1c (4 mm vs. 12.7 mm) | Subjects' glycemic control was assessed by comparing hemoglobin A1c (HbA1c) levels measured at the end of each 12 week Study Period (e.g., at Visit 5 or Visit 7) to the HbA1c measured at the start of that Study Period, i.e. the baseline (Visit 3) for Period 1 and the Period 1/2 crossover (Visit 5) for Period 2. Analysis included only subjects with HbA1C values at baseline (Visit 3) and at the end of Study Period 1 (Visit 5) and end of Period 2 (Visit 7). | Over each 12 week study period | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Glycemic Control as Measured by HbA1c, in High Dose Insulin (at Least One Dose of ≥ 40 Units) Users | Glycemic control was assessed as by difference between the subjects' HbA1c (%) at baseline (randomization, Visit 3) and at the end of each 12 week study period,in the same manner as for the primary outcome measures. The 95% confidence interval for the mean difference in HbA1c values between the 4mm PN and the longer PN will be estimated based on general linear models adjusting for baseline HbA1c. | Subjects were randomly assigned to use the BD Ultra-Fine™ 4mm pen needle for one - 12 week study period and either the BD Ultra-Fine™ 8mm pen needle or the BD Ultra-Fine™ 12.7mm pen needle for one - 12 week study period. | 
| Injection Pain Scores (4 mm vs. 8 mm) | At the end of second study period, subjects were asked to rate the level of pain experienced with study period 2 needle compared to the pen needle used in study period 1, using a 150 mm Visual Analog Scale (VAS). The VAS is a measure of the pain perceived with the needle they are using at that point in the study relative to the needle they used in Period 1. The VAS is anchored at the center (0mm) with as painful and at each extreme with much less painful (-75mm) and much more painful (+75mm); therefore a pain rating < 0 indicates that the Period 2 needle was perceived as less painful than the Period 1 needle. | At the end of Study Period 2 | 
| Injection Pain Scores (4 mm vs. 12 mm) | At the end of second study period, subjects were asked to rate the level of pain experienced with study period 2 needle compared to the pen needle used in study period 1, using a 150 mm Visual Analog Scale (VAS). The VAS is a measure of the pain perceived with the needle they are using at that point in the study relative to the needle they used the previous period. The VAS is anchored at the center (0mm) with as painful and at each extreme with much less painful (-75mm) and much more painful (+75mm); therefore a negative pain rating means the period 2 needle was perceived as less painful than the period 1 needle. | At the end of Study Period 2 | 
| Number of Serious, Unexplained Hypoglycemic Events, Reported as Number of Events by Needle. | Subjects were asked to record hypoglycemic events in his/her diary anytime his/her blood glucose (BG) was below 50mg/dL, s/he had signs/symptoms of hypoglycemia, or s/he required medical attention for treatment. Hypoglycemia was defined as serious when the subject required the assistance of another person to be treated, or when the hypoglycemic event met the per-protocol definition of a Serious Adverse Event. An unexplained episode was defined as one with no known cause (for example, the subject skipped a meal or exercised vigorously). | During Study Period 1 (12 weeks) and Study Period 2 (12 weeks) | 
| Number of Serious, Unexplained Hyperglycemic Events, Reported as Number of Events by Needle. | Subjects were asked to record hyperglycemic events in his/her diary anytime his/her blood glucose (BG) was above 400mg/dL, or s/he required medical attention for treatment for hyperglycemia. Hyperglycemia was defined as serious when the subject required the assistance of another person to be treated, or when the hyperglycemic event met the per-protocol definition of a Serious Adverse Event. An unexplained episode was defined as one with no known cause (for example, the subject missed an insulin dose). Subjects were asked to record these events in a diary. | During Study Period 1 (12 weeks) and Study Period 2 (12 weeks) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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diabetes, obesity, hypoglycemia, hyperglycemia, pen needle