Semaglutide for Low Back Pain

Official title

A Randomized-Controlled Trial of Semaglutide for Patients With Chronic Low Back Pain and Obesity

Overview

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

• Drug Semaglutide (administered by PDS290 pen-injector)
  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.
• Drug Placebo (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.

Primary outcome measures

• BPI-SF Pain Severity Scale [Time frame: Baseline, up to 52 weeks]

Secondary outcome measures (12)

• BPI-SF Pain Interference [Time frame: Baseline, up to 52 weeks]
• Oswestry Disability Index (ODI) [Time frame: Baseline, up to 52 weeks]
• SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) [Time frame: Baseline, up to 52 weeks]
• PROMIS Depression [Time frame: Baseline, up to 52 weeks]
• Pain Catastrophizing Scale [Time frame: Baseline, up to 52 weeks]
• Insomnia Severity Index [Time frame: Baseline, up to 52 weeks]
• PROMIS Sleep Disturbance [Time frame: Baseline, up to 52 weeks]
• Waist Circumference [Time frame: Baseline, up to 52 weeks]
• Number of New Concomitant Back Pain Treatments [Time frame: Baseline, up to 52 weeks]
• Change in Serum High-Sensitivity C-Reactive Protein (hs-CRP) [Time frame: Baseline, every 6 months till 52 weeks.]
• Treatment Satisfaction Questionnaire for Medication (TSQM) [Time frame: Baseline, up to 52 weeks]
• Change in serum Leptin levels [Time frame: Baseline, every 6 months till 52 weeks.]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

United States · 2 centers

• The University of Alabama at Birmingham — Birmingham
• Washington University School of Medicine — St Louis

Publications

• Smith SM, Dworkin RH, Turk DC, McDermott MP, Eccleston C, Farrar JT, Rowbotham MC, Bhagwagar Z, Burke LB, Cowan P, Ellenberg SS, Evans SR, Freeman RL, Garrison LP, Iyengar S, Jadad A, Jensen MP, Junor R, Kamp C, Katz NP, Kesslak JP, Kopecky EA, Lissin D, Markman JD, Mease PJ, O'Connor AB, Patel KV, Raja SN, Sampaio C, Schoenfeld D, Singh J, Steigerwald I, Strand V, Tive LA, Tobias J, Wasan AD, Wil PMID 32520773
• van Lennep JHPA, Trossel F, Perez RSGM, Otten RHJ, van Middendorp H, Evers AWM, Szadek KM. Placebo effects in low back pain: A systematic review and meta-analysis of the literature. Eur J Pain. 2021 Oct;25(9):1876-1897. doi: 10.1002/ejp.1811. Epub 2021 Jun 21. PMID 34051018
• Garvey WT, Frias JP, Jastreboff AM, le Roux CW, Sattar N, Aizenberg D, Mao H, Zhang S, Ahmad NN, Bunck MC, Benabbad I, Zhang XM; SURMOUNT-2 investigators. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2023 Aug 19;402(10402):613-626. doi: 10.1016/S0140-6736(23)0120 PMID 37385275
• Qaseem A, Wilt TJ, McLean RM, Forciea MA; Clinical Guidelines Committee of the American College of Physicians; Denberg TD, Barry MJ, Boyd C, Chow RD, Fitterman N, Harris RP, Humphrey LL, Vijan S. Noninvasive Treatments for Acute, Subacute, and Chronic Low Back Pain: A Clinical Practice Guideline From the American College of Physicians. Ann Intern Med. 2017 Apr 4;166(7):514-530. doi: 10.7326/M16-23 PMID 28192789
• Chiarotto A, Koes BW. Nonspecific Low Back Pain. N Engl J Med. 2022 May 5;386(18):1732-1740. doi: 10.1056/NEJMcp2032396. No abstract available. PMID 35507483
• Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap. 1994 Mar;23(2):129-38. PMID 8080219
• He Y, Xu B, Zhang M, Chen D, Wu S, Gao J, Liu Y, Zhang Z, Kuang J, Fang Q. Advances in GLP-1 receptor agonists for pain treatment and their future potential. J Headache Pain. 2025 Feb 27;26(1):46. doi: 10.1186/s10194-025-01979-4. PMID 40016636
• Samajdar SS, Bhaduri G, Ghoshal PK, Mukherjee S, Pal J, Chatterjee N, Joshi SR. Dual effects of dulaglutide on glycemic control and knee osteoarthritis pain in elderly patients with Type 2 diabetes. Pain Manag. 2024;14(7):365-373. doi: 10.1080/17581869.2024.2402214. Epub 2024 Sep 20. PMID 39301951

Identifiers

NCT: NCT07731256 · U1111-1323-5378

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗