Medication-Assisted Treatment for Youth With Substance Use Disorders

The rates of opioid use in youth are rising. Long-acting injectable naltrexone (Vivitrol), a
medication that blocks the effects of opioid drugs, has been shown to be effective for
treatment of opioid dependence in adults. Vivitrol is an important option for individuals not
wanting agonist treatment (e.g. buprenorphine, methadone). Vivitrol may be particularly
appealing to youth who have difficulty reaching their opioid use goals with daily oral
medications as it is a monthly injection and therefore eliminates the problem of daily
medication non-adherence. Vivitrol may also be appealing to families as it reduces conflicts
around issues of adherence and thus supports positive parenting. Whereas Vivitrol has been
used clinically in minors, it has not been studied in a prospective outpatient trial.
Starting naltrexone, however, can be challenging in opioid-dependent individuals because
detoxification is required prior to treatment with this medication.There are no standard
outpatient detoxification protocols for opioid-dependent youth. Therefore, more studies are
needed to support broader and approved use of Vivitrol in this population.

The purpose of this open-label pilot study is to determine the tolerability and applicability
of outpatient long-acting injectable naltrexone (Vivitrol) treatment in individuals age 16-25
("older youth") with opioid use disorder. We aim to have 16 older youth complete this trial.
Participants will undergo an outpatient detoxification / induction procedure that has been
honed over the past 13 years of work with this medication by others in our Division and is
currently being used safely in opioid-dependent adults in an ongoing clinical trial. The
detoxification / induction procedure consists of a single day of buprenorphine followed by a
washout day and 4 days of ascending oral naltrexone doses prior to administering a dose of
injectable naltrexone, typically at Day 8. Participants will then receive an additional
Vivitrol injection 4 weeks after the first; they will also receive weekly medication
management therapy with a research psychiatrist. Following the 9 week trial, participants and
are eligible for an additional third injection followed by up to 4 weeks of therapy while
proper follow-up treatment is arranged.

Primary Aim: To determine the tolerability and applicability of outpatient Vivitrol treatment
in individuals aged 16-25 ("older youth") with opioid use disorder as determined by retention
in treatment across the study. Outpatient treatment will consist of a 7-day detoxification /
naltrexone induction procedure followed by 8-weeks of treatment with Vivitrol.

Secondary Aim 1:To determine the tolerability of 7-day outpatient detoxification / naltrexone
induction for older youth as assessed by retention through first administration of Vivitrol.

Secondary Aim 2:To determine the tolerability of initial (4-week) treatment with Vivitrol as
assessed by receipt of the second Vivitrol injection at week 4.

Secondary Aim 3:To determine the safety and tolerability of Vivitrol treatment as assessed
with measures of adverse events.

Inclusion Criteria:

- Males or females 16-25 years of age

- If adult participant (>18 y/o), capacity to provide informed consent

- If minor participants (<18 y/o), capacity to assent

- If minor participants (<18 y/o), a legal guardian available to give informed consent
and accompany minor participant to all appointments or formally designate another
responsible adult to accompany the minor participant to the appointments subsequent to
the initial visit.

- DSM-5 criteria for opioid use disorder as a primary diagnosis

- Psychiatrically stable

- Physically healthy

- Voluntarily seeking outpatient opioid antagonist treatment

- Able to perform study procedures

- English speaking

Exclusion Criteria:

- History of allergy intolerance or hypersensitivity to the study medications

- Meets DSM-5 criteria for substance use disorder other than opioid use disorder as the
primary diagnosis (except nicotine or caffeine)

- Comorbid psychiatric disorder that might interfere with or make participation
hazardous, including DSM-5 diagnosis of a psychotic disorder, severe major depressive
disorder, or any psychiatric disorder that may, according to the investigator's
judgment, require either pharmacological or nonpharmacological intervention during the
course of the study

- Pregnancy, lactation within the last 6 months, or failure to use effective
contraceptive methods (condoms, diaphragm, birth control pill, IUD) in sexually active
females

- Methadone maintenance treatment or regular use of illicit methadone (>30 mg per week)

- Maintenance on, or regular use of, buprenorphine or other long-acting opioid agonists

- Current suicide risk or any suicide attempts within the past year

- Unstable medical conditions or laboratory test data, which might make participation
hazardous, such as acute hepatitis or ALT or AST > 3 times normal

- History of accidental drug overdose in the last three years defined as an episode of
opioid-induced unconsciousness or incapacitation, whether or not medical treatment was
sought or received

- Painful medical condition that requires ongoing opioid analgesia or anticipated
surgery necessitating opioid medications