Once Weekly GLP-1 in Persons With Spinal Cord Injury

• Status: Not yet recruiting
• Trial end date: 2021-12-01
• Target enrollment: 0
• Participant gender: All

Summary

Chronic spinal cord injury (SCI) results in adverse soft tissue body composition changes and an extremely sedentary lifestyle. These abrupt changes often lead to a high prevalence of cardiometabolic diseases, such as impaired glucose tolerance/diabetes mellitus and dyslipidemia, conditions which predispose those with SCI to an increased risk for cardiovascular disease compared to the general population. Due to paralysis and wheel chair dependence, maintaining an adequate level of physical activity to counteract these deleterious metabolic changes presents a unique obstacle because conventional first line interventions are lifestyle modifications (e.g., diet and exercise), which may be difficult to achieve. Recently, a new medication has been approved by the Food and Drug Administration to improve glycemic control in individuals with diabetes mellitus, and it has also been investigated as an off-label treatment to induce weight loss. Glucagon-like peptide-1 (GLP-1) agonists are a class of drugs designed to mimic the endogenous incretin hormones released from the gut in a glucose dependent manner following a meal. The mechanisms of action for this drug class of medications include stimulation of glucose-dependent insulin secretion, inhibiting glucagon release, slowed gastric emptying, and reduction of postprandial glucose excursions following food intake. In addition to improved glycemic control, this class of medications also shows promise for its non-glycemic action of facilitating weight loss. The method of delivery of the GLP-1's is by self-administered injections once daily or once weekly, depending on the severity of the clinical case and therapeutic targets for a specific patient.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: James J. Peters Veterans Affairs Medical Center
• Collaborator: Kessler Institute for Rehabilitation
• Treatments: Exenatide; Glucagon; Glucagon-Like Peptide 1

Criteria

Inclusion Criteria:

1. Male or female, age 18 to 69;

2. Chronic (e.g., duration of injury greater than 3 years) stable SCI (regardless of level of neurological injury);

3. ASIA A-D (non-ambulatory defined as not able to weight bear for more than 20% of the day);

4. Obese Percent Body Fat defined as > 25% for men and > 35% for women (as determined by screening DXA scan);

5. Insulin Resistant as determined at screening: (FPI, ≥15 µU/ml); -OR-

6. Pre-diabetic, as determined by any one of the following:

1. HbA1C ≥ 5.7% and < 6.4%; or

2. Impaired glucose tolerance by FSG ≥100 mg/dl and < 125 mg/dl and/or the 2 hour serum glucose concentration (after an OGTT) ≥ 140 mg/dl and < 200 mg/dl

Exclusion Criteria:

1. Personal history of or family history of medullary thyroid carcinoma;

2. History of multiple endocrine neoplasia syndrome type 2;

3. History of pancreatitis;

4. Existing diagnosis of diabetes mellitus, or the results from screening OGTT that identify diabetes mellitus (previously undiagnosed); laboratory thresholds for exclusion will be as follows: HbA1C ≥6.5%, fasting plasma glucose >126 mg/dl, or 2 hour value >200 mg/dl;

5. Receiving treatment for impaired glucose metabolism (i.e., insulin, secretagogues, or other agents to modify peripheral insulin sensitivity or serum glucose concentration);

6. Reduced kidney function (by glomerular filtration rate (GFR <60 ml/min) or liver function tests (any single LFT ≥ 2.5 times above the upper limit of normal) as determined by test results at screening and any time point of the study;

7. Elevated calcitonin level (as determined at screening to rule out thyroid cancer);

8. Pregnancy or women who may become pregnant during the course of the study, or those who are nursing;

9. Medically unstable;

10. Acute illness or infection;

11. Diminished mental capacity; and

12. Inability or unwillingness of subject to provide informed consent.