Chronic Lower Back Pain, glp1 Agonist, Lower Back Pain, Obesity (BMI>30)
Conditions
Keywords
Lower back pain, Obesity, Chronic Lower Back Pain, GLP1 Agonist
Brief summary
Low back pain is the leading cause of disability in the United States, and obesity is a major risk factor for its development. GLP-1 receptor agonists such as Semaglutide have emerged as effective weight loss agents that may also reduce chronic pain through weight reduction and other mechanisms. This randomized, double-blind, placebo-controlled trial will enroll 250 adults with chronic low back pain and obesity, randomized 1:1 to weekly Semaglutide 2.4 mg or placebo for 52 weeks. The primary outcome is change in low back pain severity, with secondary outcomes including pain-related disability and quality of life.
Interventions
Semaglutide 3.0 mg/mL solution for subcutaneous injection, administered using a 3 mL PDS290 pen-injector. Administered subcutaneously once weekly on the same day each week, without regard to meals. Dose escalation: 0.24 mg weekly for 28 days, then increased to 0.5 mg, 1.0 mg, 1.7 mg, and 2.4 mg every 4 weeks to reach the maintenance dose of 2.4 mg. The pen uses a drum scale of 1-80 (in increments of 1); corresponding dose counter values are: 0.24 mg = 8, 0.5 mg = 17, 1.0 mg = 34, 1.7 mg = 57, 2.4 mg = 80. Treatment duration is 52 weeks.
DRUGPlacebo (administered by PDS290 pen-injector)
Matching placebo solution for subcutaneous injection, administered using a 3 mL PDS290 pen-injector. Administered subcutaneously once weekly on the same day each week, without regard to meals, following the same escalating dose counter schedule as the active comparator (counter values: 8, 17, 34, 57, 80 every 4 weeks). Treatment duration is 52 weeks.
Sponsors
Washington University School of Medicine
Novo Nordisk A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
* Ability to provide informed consent before any trial-related activities * Age: 18-85 years * Chronic low back pain, defined as an average low back pain severity of at least 4/10 present on most days for 3 months or longer. * BMI: 30-49 kg/m2
Exclusion criteria
* Known or suspected allergy to trial medication(s), excipients, or related products * Contraindications to study medication(s), worded specifically as stated in the product's Prescribing Information * Previous randomization in this trial * Pregnant, breastfeeding, or the intention of becoming pregnant or not using adequate contraceptive measures * Low back pain related to infection, trauma, or malignancy * Plans to undergo new back pain interventions within 3 months. * Considering or have been offered surgery to treat structural disease believed to cause their low back pain, including infection, severe degeneration adjacent to a prior fusion, mobile spondylolisthesis, severe central lumbar stenosis, coronal or sagittal deformity, or other severe structural pathology diagnosed by a board-certified spine surgeon. Ambiguous cases will be adjudicated by a board-certified spine surgeon. * Another source of pain that is more severe than their low back pain (e.g., headache or radiculopathy) * History of or plans to undergo bariatric weight loss surgery * History of a major abdominal or stomach surgery that might affect drug absorption * Decrease in body weight of \> 5 kg within 3 months of screening * History of diabetes mellitus, with HbA1c \> 7 or requiring medical treatment (i.e., insulin or other diabetes medication other than Metformin). * Uncontrolled hypertension, defined as a systolic blood pressure (BP) \> 155 mmHg or a diastolic BP \> 100 mmHg * Clinically significant congestive heart failure, defined as New York Heart Association Class IV, or active symptoms related to heart failure, or exacerbation requiring hospitalization within 90 days of screening. * Any of the following: myocardial infarction, stroke, hospitalization for unstable angina pectoris, or transient ischemic attack within 90 days of screening. * Other medical conditions that could impact their treatment, similar to prior published reports * Treatment with oral or injectable glucagon-like peptide-1 (GLP-1) receptor agonists within 3 months before screening * Active acute or chronic pancreatitis diagnosed within 180 days or history of unprovoked pancreatitis within the past year. * Stage 3 or worse chronic kidney disease (i.e., eGFR \< 60). * Known active gallstone disease, other than disease previously treated with cholecystectomy. * Newly diagnosed or worsening chronic liver disease. * Active malignancy * Major neurological disease, such as multiple sclerosis or Parkinson's Disease * Major psychiatric disease, such as psychosis or schizophrenia, or a psychiatric disease requiring hospitalization in the preceding 12 months * History of a suicide attempt or any reported suicidal behavior reported within 30 days of screening. * Personal history of MEN2 * Personal or family history of medullary thyroid cancer * Impaired sensorium due to alcohol or drug use.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| BPI-SF Pain Severity Scale | Baseline, up to 52 weeks | The primary endpoint will be change in low back pain severity, measured using the 0-10 BPI-SF Pain Severity Scale. This outcome will be compared in the treatment group versus placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| BPI-SF Pain Interference | Baseline, up to 52 weeks | — |
| Oswestry Disability Index (ODI) | Baseline, up to 52 weeks | — |
| SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) | Baseline, up to 52 weeks | — |
| PROMIS Depression | Baseline, up to 52 weeks | — |
| Pain Catastrophizing Scale | Baseline, up to 52 weeks | — |
| Insomnia Severity Index | Baseline, up to 52 weeks | — |
| PROMIS Sleep Disturbance | Baseline, up to 52 weeks | — |
| Waist Circumference | Baseline, up to 52 weeks | — |
| Number of New Concomitant Back Pain Treatments | Baseline, up to 52 weeks | The number and type of new low back pain treatments initiated during the study period, captured using the study's Concomitant Back Pain Treatment Log. New daily pain medications, exercise/therapy regimens, cognitive/behavioral interventions, spinal injections, interventional pain procedures, lumbar spine surgery, and other treatments. |
| Change in Serum High-Sensitivity C-Reactive Protein (hs-CRP) | Baseline, every 6 months till 52 weeks. | Serum hs-CRP will be measured at each time point and reported in mg/L. Additional exploratory inflammatory blood biomarkers may also be assessed to characterize systemic inflammation. |
| Treatment Satisfaction Questionnaire for Medication (TSQM) | Baseline, up to 52 weeks | — |
| Change in serum Leptin levels | Baseline, every 6 months till 52 weeks. | Serum leptin will be measured at each time point and reported in ng/mL. |
Countries
United States
Contacts
CONTACTElizabeth Wilson, MS, CCRP
CONTACTFaraz Arkam, MD
PRINCIPAL_INVESTIGATORJacob K Greenberg, MD, MSCI
Washington University School of Medicine
PRINCIPAL_INVESTIGATORBurel R Goodin, PhD
Washington University School of Medicine
Outcome results
None listed