Building on breakthrough findings from a residential treatment study, Penn State researchers are launching a pivotal clinical trial to investigate semaglutide's potential in treating opioid use disorder (OUD) in outpatient settings. The initiative follows successful preliminary research that demonstrated significant reductions in opioid cravings using another GLP-1 receptor agonist, liraglutide.
Previous Success Paves Way for New Investigation
The foundational pilot study, conducted at Caron Treatment Centers under UG3 DA050325, yielded remarkable results with liraglutide. The double-blind, placebo-controlled trial showed significant reduction in opioid cravings even at the lowest doses administered (Cohen's d = .5, p=0.005). Notably, the study revealed that liraglutide-treated patients maintained stable craving levels during high-stress periods, unlike the placebo group where stress correlated with increased cravings (p=.031).
New Outpatient Trial Design and Objectives
The new study expands the scope to outpatient settings, where most addiction treatment occurs. This randomized, double-blind, placebo-controlled trial will evaluate semaglutide's effectiveness over 12 weeks in patients receiving either methadone or buprenorphine/naloxone maintenance treatment.
The trial design includes:
- 200 participants divided across four arms
- Weekly subcutaneous administration starting at 0.25 mg
- Dose optimization up to 1.0 mg based on tolerability
- 19-week total study duration including follow-up
Primary and Secondary Endpoints
The study's primary focus is measuring abstinence from illicit and nonprescribed opioids, verified through both urine testing and Timeline FollowBack reporting. Secondary endpoints include:
- Real-time craving assessments via smartphone surveys
- Weekly in-person craving evaluations
- Sustained abstinence measurements
- Stimulant abstinence monitoring
- Correlation analysis between craving and abstinence measures
Expansion Plans and Funding Needs
While three trial sites are confirmed for a January 2025 start, researchers are seeking to add Stanley Street Treatment & Resources (SSTAR) as a fourth location. SSTAR's extensive patient base - including 500 methadone and 800 buprenorphine patients - would significantly enhance the study's statistical power.
"This study could deliver breakthrough, field-changing results," notes Dr. Grigson. "Adding a fourth site would substantially increase our ability to demonstrate statistical significance, particularly important given that our patient population is already receiving craving suppression through standard care."
The expansion requires $861,000 in direct costs, with researchers actively seeking funding partners to support this critical addition to the study infrastructure.
Potential Impact on OUD Treatment
If successful, this research could lead to the first FDA-approved OUD treatment in decades that operates independently of the opioid system. This novel approach could provide a crucial new tool in addressing the ongoing opioid crisis, particularly significant given its potential to reduce both cravings and relapse risk through a different biological pathway than current treatments.
