Evaluation of Doxazosin to Alter the Abuse of Oxycodone

Phase 2

Terminated

Conditions: Opioid-use Disorder

Interventions: Drug: Intranasal Oxycodone
Behavioral: Cue Session

Registration Number: NCT03415581

Lead Sponsor: New York State Psychiatric Institute

Brief Summary: Healthy, adult men and women, aged 21 to 59 years, who abuse opioids and are physically dependent on them will be recruited to participate in a study to examine the ability of doxazosin, an epinephrine receptor blocker, to alter the abuse potential of oxycodone. After participants complete the screening process, they will be scheduled for inpatient admission onto our clinical inpatient where they will reside during the 8-week study. During Weeks 1-2, participants will be transitioned from their normal opioid use regime onto oral morphine until withdrawal dissipates. At this time participants will also be stabilized on the first dose of doxazosin (0 or 16 mg/day; active doxazosin will be started at 4 mg and increased by 4 mg every 3 days). During Weeks 3-4, either active or placebo oxycodone will be available (in random order). Monday-Friday each these drugs will be tested using our sample and choice self-administration procedure. On Friday, participants will also complete a cue exposure session during which they will be presented drug cues to determine whether the study medication affects how participants react to them. To summarize, Weeks 1-2 and 5-6 will be stabilization weeks (0 or 16 mg doses of doxazosin administered in random order) and Weeks 3-4 and 7-8 will be test weeks under each of the doxazosin maintenance doses. At the conclusion of the study, participants will be given an exit interview, warnings about re-initiation of opioid use, and counseling about the different treatment options for Opioid Use Disorder. Within 1 week after discharge, investigators will assess adverse events using the a number of clinical assessments. At each weekly visits, investigators will assess participants' interest in treatment and drug use patterns.

Detailed Description: Healthy, adult men and women, aged 21 to 59 years, who abuse opioids and are physically dependent on them will be recruited to participate in a study to examine the ability of doxazosin, an alpha-1 adrenergic receptor antagonist, to alter the abuse liability of oxycodone. After participants complete the screening process, they will be scheduled for admission onto the General Clinical Research Unit on 5-South where they will reside during an 8-week study . During Weeks 1-2, participants will be stabilized on morphine and the first dose of doxazosin (0 or 16 mg/day; active doxazosin will be started at 4 mg and increased by 4 mg every 3 days; dosing will occur at 8pm each evening). During the stabilization periods, participants will be treated for emergent withdrawal symptoms with supplemental medications until withdrawal symptoms have dissipated.

During Weeks 3-4, either active or placebo oxycodone will be available (order of testing active or placebo oxycodone will be randomized). During active oxycodone weeks, participants will receive a sample dose of intransasal (IN) oxycodone (0, 12.5, 25, 50, or 100 mg/70kg) during morning sessions on Monday-Friday. The sampled reinforcer will be available during afternoon choice sessions using a modified progressive ratio self-administration procedure. During placebo oxycodone weeks, participants will receive a sample dose of placebo oxycodone (0 mg/70kg) during morning sessions on Monday-Thursday followed by afternoon choice sessions. On Friday, participants will receive 25 mg IN oxycodone during a sample session (the oxycodone dose on Fri morning will always be active). When self-administering oxycodone, participants will be instructed to insufflate the entire dose through one or both nostrils within 5-10 seconds. Following the sample session on Fri, participants will complete a cue exposure session during which they will be presented with neutral cues followed by drug cues. This procedure will allow the investigators to determine whether the study medication affects reactivity to drug-related cues after a period of no oxycodone availability. After the cue exposure session on Fri, participants will be given the opportunity to self-administer oxycodone. To summarize, Weeks 1-2 and 5-6 will be stabilization weeks (0 or 16 mg doses of doxazosin administered in random order) and Weeks 3-4 and 7-8 will be test weeks under each of the doxazosin maintenance doses. At the conclusion of the study, participants will be given an exit interview during which the study will be described. Those who are interested in treatment for their drug use at the end of the study will be offered referrals to studies at our Substance Treatment and Research Service or other treatment providers. Within 1 week after discharge, investigators will assess adverse events, pregnancy (using a urine pregnancy test), general health (complete blood count, blood chemistry, urinalysis, blood pressure, heart rate, body weight, EKG), and suicide (Columbia Suicide Severity Rating Scale).

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 13

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Doxazosin (Placebo First)	Intranasal Oxycodone	Maintenance on a daily dose of oral doxazosin (0 mg) for 4 weeks, followed by 4-week maintenance on active doxasozin (up to 16mg/day or the highest tolerated dose. During this time subjects complete testing sessions (Self-administration, Cue session) assessing the abuse potential of intranasal oxycodone.
Doxazosin (Placebo First)	Cue Session	Maintenance on a daily dose of oral doxazosin (0 mg) for 4 weeks, followed by 4-week maintenance on active doxasozin (up to 16mg/day or the highest tolerated dose. During this time subjects complete testing sessions (Self-administration, Cue session) assessing the abuse potential of intranasal oxycodone.
Doxazosin (Active First)	Cue Session	Maintenance on a daily dose of oral doxazosin (16 mg, or the highest tolerated dose) for 4-weeks, followed by 4-week maintenance on placebo doxasozin. During this time subjects complete testing sessions (Self-administration, Cue session) assessing the abuse potential of intranasal oxycodone.
Doxazosin (Active First)	Intranasal Oxycodone	Maintenance on a daily dose of oral doxazosin (16 mg, or the highest tolerated dose) for 4-weeks, followed by 4-week maintenance on placebo doxasozin. During this time subjects complete testing sessions (Self-administration, Cue session) assessing the abuse potential of intranasal oxycodone.

Primary Outcome Measures

Name	Time	Method
Opioid Self-administration	Averaged across the 8-week trial.	Clinical laboratory task where the participant is asked to choose between drug and money. Shown as the mean percent of drug choices.

Secondary Outcome Measures

Name	Time	Method
Opioid Craving	Averaged across the 8-week trial.	Self-reported craving for opioid drugs. Participants are asked to indicate the extent to which they agree with the phrase "I want opioids" on a scale of 0 (Not-at-All) to 100 (Completely).