Once Weekly GLP-1 in Persons With Spinal Cord Injury

March 10, 2023 updated by: William A. Bauman, M.D., James J. Peters Veterans Affairs Medical Center

The Efficacy of a Once Weekly Glucagon-Like Peptide-1 Agonist on Body Weight/Composition and Metabolic Parameters in Persons With SCI

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
5

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • New Jersey
      • West Orange, New Jersey, United States, 07052
        • Kessler Institute for Rehabilitation

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 69 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Semaglutide 1MG Injection [Ozempic]
20 subjects will be randomized to receive once weekly injection of Semaglutide (Ozempic1mg) for 26 weeks.
Drug: Semaglutide 1MG Injection [Ozempic]
Once weekly injection of 1mg of Semaglutide.
Other: No Intervention
10 subjects will be randomized to receive no intervention for 26 weeks.
Other: No Intervention
No injection will be administered

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Body Weight
Time Frame: Baseline, Week 13, Week 26
Efficacy of GLP-1 to reduce total body weight determined by Dual Energy Absorptiometry (DXA)
Baseline, Week 13, Week 26
Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)
Time Frame: Baseline, Week 13, Week 26
Efficacy of GLP-1 to reduce HOMA-IR
Baseline, Week 13, Week 26
Homeostatic Model Assessment of Beta-Cell Function (HOMA-B)
Time Frame: Baseline, Week 13, Week 26
Efficacy of GLP-1 to increase HOMA-B
Baseline, Week 13, Week 26

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Body Fat
Time Frame: Baseline, Week 13, Week 26
Efficacy of GLP-1 to reduce total body fat determined by Dual Energy Absorptiometry (DXA)
Baseline, Week 13, Week 26
Glycated Hemoglobin (HbA1C)
Time Frame: Baseline, Week 13, Week 26
Efficacy of GLP-1 to reduce HbA1C
Baseline, Week 13, Week 26

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
James J. Peters Veterans Affairs Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Kessler Institute for Rehabilitation

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 16, 2018

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2020

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 1, 2023

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 20, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 20, 2017

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 25, 2017

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 14, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 10, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BAU-17-038

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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