Evaluation of Doxazosin to Alter the Abuse of Oxycodone
Condition: Opioid-use Disorder
MeSH terms: Opioid-Related Disorders
Intervention: Intranasal Oxycodone; Cue Session
Intervention description: Under each doxazosin maintenance condition the effects of intranasal oxycodone will be assessed in order to determine if doxazosin reduces dependent measures assessing its abuse potential.; During the cue exposure session participants are presented with neutral cues followed by drug-related cues. This procedure will allow the investigators to determine whether the study medication affects reactivity to drug-related cues.
Intervention MeSH terms: Oxycodone
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Enrollment: 13.0
Sex: All
Minimum age: 21 Years
Maximum age: 59 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        Participants must meet all of the following inclusion criteria to be enrolled into the
        study:

          1. 21-59 years of age. Ascertained by: Self-reported age and/or verification with legal
             identification.

          2. Diagnostic criteria for Opioid Use Disorder moderate-severe (304.00) as per DSM-V
             Ascertained by: Clinical interviews (telephone, psychologist, nurse, physician),
             naloxone challenge test/visual evidence of opioid withdrawal.

          3. No current or past diagnosis of schizophrenia, schizoaffective disorder, or other
             psychotic disorder; bipolar I or bipolar II disorder, other major mood, psychotic, or
             anxiety disorder that might interfere with the study. Ascertained by: Clinical
             interview with physician or nurse.

          4. Physically healthy. Ascertained by: Clinical interview with physician, laboratory
             tests (urinalysis, blood chemistry, 12-lead ECG), physical examination, self-reported
             medical history.

          5. Able to perform study procedures. Ascertained by: Practice session or Clinical
             Judgement (Psychologist or Physician)

          6. Normal body weight. Ascertained by: Body Mass Index <30.

          7. Current or history of intranasal opioid use. Ascertained by: Clinical interviews
             (telephone, psychologist, and psychiatric NP, or physician).

          8. Current intranasal or intravenous use of opioids in amounts and/or frequencies that
             meet or exceed those used in the proposed study (e.g., 3-4 tablets of a prescription
             opioid medication per day or 1-2 bags of heroin per day). Ascertained by: Clinical
             interviews (telephone, psychologist, psychiatric NP, or physician)

          9. If female and using oral contraceptives, must use alternative forms of contraception
             as well (e.g. condoms in combination with spermicide). Ascertained by: Clinical
             interviews (telephone, psychologist, nurse, physician), physical examination.

         10. Has not participated in another opioid laboratory study within the past 3 months.
             Ascertained by: Clinical interviews (psychologist physician, or psychiatric NP),
             review of laboratory records.

        Participants will be excluded from study participation if they meet any of the following
        exclusion criteria:

          1. Meeting DSM-V criteria for substance use disorder (moderate-severe) on drugs other
             than opioids, nicotine or caffeine (must be less than 500 mg caffeine daily).
             Ascertained by: Clinical interview with physician or psychiatric NP, urine screen,
             observation.

          2. Participants requesting treatment. Ascertained by: Self-report during interview.

          3. Treatment with any investigational drug during the last 30 days. Ascertained by:
             Self-report during interview.

          4. Participants on parole or probation. Ascertained by: Self-report during interview,
             criminal background check upon admission.

          5. Currently pregnant or trying to conceive, or currently lactating. Ascertained by:
             Blood pregnancy testing at screening, on admission and (beta hCG), and self-report
             during interview and study visits.

          6. Current or recent history of significant violent or suicidal behavior and/or
             suicidal/homicidal risk. Ascertained by: Clinical interview with a psychiatrist or
             psychiatric NP, and C-SSRS, MINI, and Beck Depression Inventory (based on current
             state and history).

          7. Cannot read or understand the self-report assessment forms unaided, or are so severely
             disabled that they cannot comply with the requirements of the study. Ascertained by:
             Clinical interview (psychologist, physician, or psychiatric NP), or practice session.

          8. Elevated liver function tests (i.e., AST and ALT > 3 times the upper limit of normal
             (ULN); bilirubin > 2x ULN; hepatitis B or chronic hepatitis C). Ascertained by:
             Laboratory tests.

          9. Physical disorders that might make participation hazardous such as AIDS, cancer,
             baseline hypotension, orthostatic hypotension or syncope, hypertension (blood pressure
             > 140/90), uncontrolled diabetes, pulmonary hypertension or heart disease (please note
             that participants will be asked about previous visits to a cardiologist, chest pain,
             or strong palpitations; if these exist, they will be referred to a cardiologist and
             excluded unless cleared for participation by a cardiologist). Ascertained by: Clinical
             interview (psychologist, physician, or psychiatric NP) physical examination, 12-lead
             ECG.

         10. Current major Axis I psychopathology other than opioid use disorder (e.g., mood
             disorder with functional impairment or suicide risk, schizophrenia), that might
             interfere with ability to participate in the study. Ascertained by: Clinical
             interviews (psychologist, physician, or psychiatric NP).

         11. Sensitivity, allergy, or contraindication to opioids, doxazosin, adrenergic
             antagonists or agonists, or similar compounds. Ascertained by: Clinical interview
             (psychologist, physician, or psychiatric NP).

         12. Planning to conceive within 6 months of study participation. Ascertained by: Clinical
             interview (psychologist, physician, or psychiatric NP).

         13. Use of any prescription, over-the-counter medication that affects CYP3A4 activity are
             prohibited for at least 7 days prior to the anticipated study start date; or the use
             of phosphodiesterase inhibitors and MAOIs 14 days prior to the study. Ascertained by:
             Medical History, Clinical Interview ((psychologist, physician, or psychiatric NP).