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Study Protocol for a Prospective, Multicenter, Randomized, Open-Label, Parallel-Group Clinical Trial Comparing the Efficacy and Safety of a Needle-Free Insulin Injector and a Conventional Insulin Pen in Controlling Blood Glucose Concentrations in Chinese Patients with Type 2 Diabetes Mellitus (The FREE Study)

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Abstract

Introduction

China has the largest number of diabetic patients in the world. In the past 2 decades, the prevalence of diabetes in China has increased dramatically, and the current status of diabetes control in the diabetic population is not satisfactory. Although insulin is currently recognized in diabetes treatment guidelines as the therapeutic option for patients not adequately controlled by diet/exercise and oral agents, the proportion of patients with type 2 diabetes using insulin is still very low, and the time when insulin therapy is initiated is relatively late. In using insulin injections, concerns about the complexity of the treatment regimen, a fear of needles, and other psychological barriers can affect insulin treatment, impacting on patient compliance and potentially resulting in a poor treatment response. Another type of insulin injection device that has become available recently, the needle-free injector, is now being used in clinical practice because of its unique features and patients’ injection experiences. The aims of this study are to investigate the efficacy and safety of the needle-free injector-based insulin treatment in blood glucose control in patients with type 2 diabetes, as compared with a conventional needle-based insulin treatment, and to evaluate patient satisfaction with the different insulin delivery methods.

Methods and Planned Outcomes

A prospective, multicenter, randomized, open-label, parallel-group clinical trial was designed and implemented in China. A total of 420 patients with type 2 diabetes from ten research centers will be enrolled in the study. The primary efficacy endpoint is the change in the glycosylated hemoglobin (HbA1c) level from baseline to after 16 weeks of treatment after randomization. Secondary efficacy endpoints include measurements of blood glucose concentrations, the rate of achieving the target HbA1c level of less than 7%, patients’ quality-of-life (as determined by the SF-36 questionnaire), the insulin dose administered, compliance with insulin therapy, and patients’ satisfaction with their injection device.

Ethics and Dissemination

The study was approved by the Independent Ethics Committee (IEC) of Peking University Peoples Hospital and was conducted in accordance with the moral, ethical, and scientific principles of the declaration of Helsinki and the provisions of good clinical practice (GCP) in China. Written informed consent will be obtained from all participants before any study-related procedures are implemented. It is hoped that the study will provide evidence for the clinical application of the needle-free injector by providing data on its efficacy and safety, as compared with a conventional insulin pen, in the Chinese type 2 diabetes population. When available, the results will be published in an international peer-reviewed journal.

Trial Registration

ClinicalTrials.gov Identifier, NCT03243903. Registration date, August 9, 2017.

Funding

Beijing QS Medical Technology Co., Ltd.

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References

  1. IDF Diabetes Atlas, 8th edition, 2017. https://www.idf.org/e-library/epidemiology-research/diabetes-atlas/134-idf-diabetes-atlas-8th-edition.html. Accessed 1 Jan 2019.

  2. Hu C, Jia W. Diabetes in China: epidemiology and genetic risk factors and their clinical utility in personalized medication. Diabetes. 2018;67:3–11.

    Article  CAS  PubMed  Google Scholar 

  3. Chinese Diabetes Society Diabetes Education and Management Group. Type 2 diabetes self-management prescription expert consensus in China. Chin J Diabetes Mellit. 2017;9(12):740–50.

    Google Scholar 

  4. Kahn SE, Haffner SM, Heise MA, et al. Glycemic durability of rosiglitazone, metformin, or glyburide monotherapy. N Engl J Med. 2006;355:2427–43.

    Article  CAS  PubMed  Google Scholar 

  5. Koro CE, Bowlin SJ, Bourgeois N, Fedder DO. Glycemic control from 1988 to 2000 among US adults diagnosed with type 2 diabetes: a preliminary report. Diabetes Care. 2004;27:17–20.

    Article  PubMed  Google Scholar 

  6. Turner RC, Cull CA, Frighi V, Holman RR, UK Prospective Diabetes Study (UKPDS) Group. Glycemic control with diet, sulfonylurea, metformin, or insulin in patients with type 2 diabetes mellitus: progressive requirement for multiple therapies (UKPDS 49). JAMA. 1999;281:2005–12.

    Article  CAS  PubMed  Google Scholar 

  7. Rwegerera GM, Moshomo T, Gaenamong M, et al. Health-related quality of life and associated factors among patients with diabetes mellitus in Botswana. Alex J Med. 2018;54:111–8.

    Article  Google Scholar 

  8. Polonsky WH, Fisher L, Guzman S, et al. Psychological insulin resistance in patients with type 2 diabetes: the scope of the problem. Diabetes Care. 2005;28:2543–5.

    Article  PubMed  Google Scholar 

  9. Korytkowski M, Niskanen L, Asakura T. FlexPen: addressing issues of confidence and convenience in insulin delivery. Clin Ther. 2005;27(Suppl B):S89–100.

    Article  PubMed  Google Scholar 

  10. Baruah MP, Kalra S, Bose S, Deka J. An audit of insulin usage and insulin injection practices in a large Indian cohort. Indian J Endocrinol Metab. 2017;21:443–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Ji L, Sun Z, Li Q, et al. Lipohypertrophy in China: prevalence, risk factors, insulin consumption, and clinical impact. Diabetes Technol Ther. 2017;19:61–7.

    Article  CAS  PubMed  Google Scholar 

  12. Hu J, Shi H, Zhao C, et al. Lispro administered by the QS-M needle-free jet injector generates an earlier insulin exposure. Expert Opin Drug Deliv. 2016;13:1203–7.

    Article  CAS  PubMed  Google Scholar 

  13. Guo L, Xiao X, Sun X, Qi C. Comparison of jet injector and insulin pen in controlling plasma glucose and insulin concentrations in type 2 diabetic patients. Medicine. 2017;96:e5482 (Baltimore).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Ji L, Zhang P, Weng J, et al. Observational registry of basal insulin treatment (ORBIT) in patients with type 2 diabetes uncontrolled by oral hypoglycemic agents in China—study design and baseline characteristics. Diabetes Technol Ther. 2015;17:735–44.

    Article  CAS  PubMed  Google Scholar 

  15. Sarno MJ, Bell J, Edelman SV. Pharmacokinetics and glucodynamics of rapid-, short-, and intermediate-acting insulins: comparison of jet injection to needle syringe. Diabetes Technol Ther. 2002;4:863–6.

    Article  CAS  PubMed  Google Scholar 

  16. Engwerda EE, Abbink EJ, Tack CJ, de Galan BE. Improved pharmacokinetic and pharmacodynamic profile of rapid-acting insulin using needle-free jet injection technology. Diabetes Care. 2011;34:1804–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. de Galan BE, Engwerda EE, Abbink EJ, Tack CJ. Body mass index and the efficacy of needle-free jet injection for the administration of rapid-acting insulin analogs, a post hoc analysis. Diabetes Obes Metab. 2013;15:84–6.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We thank all the researchers and participants who have participated in this study.

Funding

This study and the article processing charges were funded by Beijing QS Medical Technology Co., Ltd. However, Beijing QS Medical Technology Co. was not involved in the study design, data collection, analysis and interpretation, article writing, or the decision to submit for publication. All authors had full access to raw data, and the corresponding author has final responsibility for submission for publication.

Authorship

All named authors meet the International Committee of Medical Journal Editors (ICMJE) criteria for authorship for this article, take responsibility for the integrity of the work as a whole, and have given their approval for this version to be published.

Authorship Contributions

LiNong Ji contributed to the conception and design of the study, developed the study protocol, was responsible for the recruitment and follow-up of the patients enrolled, wrote the protocol manuscript, and will also contribute to the analysis and interpretation of data. All authors will have full access to all the data in this study and will take complete responsibility for the integrity of the data and the accuracy of the data analyses. All authors will read and approve the final manuscript that is submitted.

Disclosures

Linong Ji receives consulting fees from Beijing QS Medical Technology Co. Ltd. LiMing Chen, YanGang Wang, ZhongShu Ma, XingWu Ran, ZiLin Sun, XiangJin Xu, GuiXia Wang, LiXin Guo, and ZhongYan Shan have nothing to disclose.

Compliance with Ethics Guidelines

The study was approved by the Independent Ethics Committee (IEC) of Peking University Peoples Hospital and was conducted in accordance with the moral, ethical, and scientific principles of the declaration of Helsinki and the provisions of good clinical practice (GCP) in China. Written informed consent will be obtained from all participants before any study-related procedures are implemented. It is hoped that the study will provide evidence for the clinical application of the needle-free injector by providing data on its efficacy and safety, as compared with a conventional insulin pen, in the Chinese type 2 diabetes population. When available, the results will be published in an international peer-reviewed journal.

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Correspondence to LiNong Ji.

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Ji, L., Chen, L., Wang, Y. et al. Study Protocol for a Prospective, Multicenter, Randomized, Open-Label, Parallel-Group Clinical Trial Comparing the Efficacy and Safety of a Needle-Free Insulin Injector and a Conventional Insulin Pen in Controlling Blood Glucose Concentrations in Chinese Patients with Type 2 Diabetes Mellitus (The FREE Study). Adv Ther 36, 1485–1496 (2019). https://doi.org/10.1007/s12325-019-00951-4

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