# Phase III double-blind, randomized controlled trial of suvorexant versus placebo to treat insomnia in persons with opioid use disorder

> **NIH NIH U01** · JOHNS HOPKINS UNIVERSITY · 2024 · $6,175,490

## Abstract

Opioid use disorder (OUD) is a rapidly escalating public health crisis with recent evidence suggesting that
close to 70% of drug overdose deaths involved opioids in the last year. Medications for OUD (MOUDs) such as
buprenorphine and methadone are the frontline treatment for OUD, yet over half of individuals who initiate
MOUD relapse or leave treatment in the first year, highlighting the importance of adjunctive therapies that
might improve OUD treatment outcomes. Insomnia is a common and often recalcitrant issue among persons
on MOUDs but there is little guidance on how to ameliorate symptoms of insomnia during OUD treatment. The
orexin (or hypocretin) neurotransmitter system plays a role in insomnia and in the onset, progression, and
maintenance of OUD. Suvorexant is a dual-orexin receptor antagonists that is FDA-approved for the treatment
of insomnia, and data from our group suggests that suvorexant might be especially efficacious in treating
insomnia in persons with OUD and may also confer collateral benefits including decreased opioid craving and
symptoms of withdrawal. Moreover, suvorexant has an excellent safety profile and did not result in increased
adverse events or measures of abuse potential when compared to placebo in our pilot study. The proposed
study is an FDA-regulatory-grade Phase III multisite randomized-controlled trial of suvorexant versus placebo
in persons with insomnia who are utilizing long-term MOUD treatment. Participants who are prescribed
buprenorphine or methadone for OUD will be screened to determine study eligibility. Eligible individuals will be
enrolled for an 8-week study that includes the following conditions: one night double-dummy placebo lead-in
prior to randomization; ~8 weeks of suvorexant or placebo where the dose may be escalated from 10 mg to 20
mg after 3 nights (consistent with current suvorexant label instructions); and two-nights double-dummy placebo
lead-out to examine discontinuation effects. In lab polysomnography (PSG) will be used to at the beginning
and end of the trial to determine the primary endpoint of change from baseline total sleep time. Adverse events
and other indicators of patient safety will be monitored throughout the study. Participants will also be assessed
for OUD treatment outcomes including regular urine toxicology and trajectories of mental health during the
study. Specific Aims of the study are to (Aim 1) evaluate the efficacy of suvorexant versus placebo in treat
insomnia in persons taking buprenorphine or methadone for OUD treatment, (Aim1) Evaluate the safety of
suvorexant versus placebo in persons taking buprenorphine or methadone for OUD treatment, (Aim 3) submit
a Supplement Application of Efficacy to the FDA to support an update to the label of suvorexant, and
(Exploratory Aim 4) determine whether suvorexant versus placebo improves OUD treatment outcomes. The
results of this important study will inform treatment providers on whether suvorexant is safe and effective fo...

## Key facts

- **NIH application ID:** 10916717
- **Project number:** 1U01DA060708-01
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Andrew S Huhn
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $6,175,490
- **Award type:** 1
- **Project period:** 2024-05-15 → 2027-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10916717

## Citation

> US National Institutes of Health, RePORTER application 10916717, Phase III double-blind, randomized controlled trial of suvorexant versus placebo to treat insomnia in persons with opioid use disorder (1U01DA060708-01). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10916717. Licensed CC0.

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