Once Weekly GLP-1 in Persons With Spinal Cord Injury
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|ClinicalTrials.gov Identifier: NCT03292315|
Recruitment Status : Not yet recruiting
First Posted : September 25, 2017
Last Update Posted : September 26, 2017
|Condition or disease||Intervention/treatment||Phase|
|Spinal Cord Injuries Insulin Resistance Pre Diabetes Obesity||Drug: Exenatide 2 MG Injection [Bydureon] Other: No Intervention||Phase 4|
Obesity is an underlying condition that predisposes to the development of several medical disorders and diseases. It is well appreciated that obesity has reached pandemic proportions in Western societies. The World Health Organization (WHO) estimates that 1.9 billion adults worldwide are overweight and 600 million of these individuals are further sub-classified as obese, with a 44% estimated burden for type 2 diabetes mellitus (T2DM) being attributed to being overweight/obese, as well as a 23% estimated burden for heart disease ("Obesity and overweight," 2016). Excess adipose tissue is assumed to play an integral role in the pathogenesis of vascular dysfunction and the development of T2DM (Lau, Dhillon, Yan, Szmitko, & Verma, 2005).
During the acute and chronic phases of SCI, marked adverse changes occur in soft tissue body composition and associated carbohydrate and lipid metabolism. After an initial rapid loss of lean tissue below the neurological level of injury, a more insidious and progressive lean tissue loss is observed (Modlesky et al., 2004; Spungen et al., 2003), which is accompanied by an increased total body adiposity (Spungen et al., 2003), with accumulation of fat in the abdominal (e.g., visceral) compartment (Gorgey, Mather, Poarch, & Gater, 2011). These adverse changes to body composition contribute to, and are associated with, a higher prevalence of insulin resistance and disorders of carbohydrate metabolism (e.g., impaired glucose tolerance and T2DM) than that reported in the general population (Bauman & Spungen, 1994). The primary approach to treat T2DM in the general population is diet and exercise (i.e., lifestyle modification). Of note, the profound inactivity and adverse soft tissue body composition changes that occur in individuals after SCI result in metabolic morbidity which is extremely difficult to manage with lifestyle modification alone. Conventional therapeutic strategies employed in the adjunctive treatment of carbohydrate metabolism disorders in the general population include several pharmacological approaches to maintain and improve glycemic control are in standard practice and include reducing the serum glucose concentration (i.e., insulin, sulphonylureas, thiazolidinediones or glitazones), suppressing hepatic gluconeogenesis (i.e., insulin, biguanides), stimulating endogenous insulin secretion (i.e., sulphonylureas), and/or by inhibiting glucose renal reabsorption and increasing glycosuria (i.e., SGLT-2 inhibitors).
In 2005 a new class of drugs was approved for the treatment for T2DM by targeting the GLP-1 receptor. Exenatide is a GLP-1 agonist that acts as an incretin hormone, and it belongs to a class of gastrointestinal hormones which are released from the L cells of the intestines in response to food ingestion that, as one of its mechanisms of action, increase insulin secretion from pancreatic beta cells (Vilsboll et al., 2003). This phenomenon that was coined "the incretin effect" in the 1960's described the significantly higher plasma insulin levels following orally versus intravenously administered glucose, which can account for 50 to 70% of the insulin secretion observed after food intake (Baggio & Drucker, 2007). Treatment with GLP-1's has increased over the past several years because of their mechanism of action to increase insulin secretion, inhibit glucagon release in a glucose-dependent manner, thus minimizing the risk for hypoglycemia (Baggio & Drucker, 2007; Nauck, Stockmann, Ebert, & Creutzfeldt, 1986; Vilsboll, Krarup, Madsbad, & Holst, 2002). Numerous multi-ethnic and multi-national trials have been performed with exenatide, but none have been reported in persons with SCI. Previous investigation with exenatide once-weekly in able-bodied individuals has resulted in weight loss ranging from 1.6 to 3.9 kg following 24 weeks of intervention (Bergenstal et al., 2010; Blevins et al., 2011; Buse et al., 2013; Chiquette, Toth, Ramirez, Cobble, & Chilton, 2012; Davies et al., 2013; Diamant et al., 2010; Drucker et al., 2008; Inagaki, Atsumi, Oura, Saito, & Imaoka, 2012; Ji et al., 2013; Russell-Jones et al., 2012). As such, to date there is no evidence of the potential efficacy of exenatide to result in weight loss, improve glycemic control, and/or reduce insulin resistance in persons with SCI.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||The Efficacy of a Once Weekly Glucagon-Like Peptide-1 Agonist on Body Weight/Composition and Metabolic Parameters in Persons With SCI|
|Estimated Study Start Date :||February 2018|
|Estimated Primary Completion Date :||December 2021|
|Estimated Study Completion Date :||December 2021|
Experimental: Exenatide 2 MG Injection [Bydureon]
20 subjects will be randomized to receive once weekly injection of Exenatide (Bydureon 2mg) for 26 weeks.
Drug: Exenatide 2 MG Injection [Bydureon]
Once weekly injection of 2mg of Exenatide
10 subjects will be randomized to receive no intervention for 26 weeks.
Other: No Intervention
No injection will be administered
- Body Weight [ Time Frame: Baseline, Week 13, Week 26 ]Efficacy of GLP-1 to reduce total body weight determined by Dual Energy Absorptiometry (DXA)
- Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) [ Time Frame: Baseline, Week 13, Week 26 ]Efficacy of GLP-1 to reduce HOMA-IR
- Homeostatic Model Assessment of Beta-Cell Function (HOMA-B) [ Time Frame: Baseline, Week 13, Week 26 ]Efficacy of GLP-1 to increase HOMA-B
- Body Fat [ Time Frame: Baseline, Week 13, Week 26 ]Efficacy of GLP-1 to reduce total body fat determined by Dual Energy Absorptiometry (DXA)
- Glycated Hemoglobin (HbA1C) [ Time Frame: Baseline, Week 13, Week 26 ]Efficacy of GLP-1 to reduce HbA1C
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03292315
|Contact: Joshua C Hobson, M.S.||718-584-9000 ext email@example.com|
|Contact: Michael LaFountaine, Ed.D.||718-584-9000 ext firstname.lastname@example.org|
|United States, New Jersey|
|Kessler Institute for Rehabilitation|
|West Orange, New Jersey, United States, 07052|
|Contact: Christopher M Cirnigliaro, M.S. 973-731-3900 ext 2755 email@example.com|
|Sub-Investigator: Christopher M Cirniliaro, M.S.|