Clonidine for Sleep Disturbances in Children With Autism Spectrum Disorder

Inclusion Criteria:

- outpatients between 6-14 years of age, inclusive, from underserved populations (i.e.,
Low SES, racial and ethnic minorities, rural populations);

- diagnosis of Autism Spectrum Disorder based on DSM-V criteria and the ATN assessment
protocol;

- mental age ≥ 24 months as determined by the Stanford Binet-Fifth Edition (SB-5) or
Mullen Scales of Early Learning (MSEL) (the child must be of a mental age to
understand the BI/SH protocol);

- significant sleep disturbance as determined the CSHQ 33-item Total Score of ≥ 48 and
one of the following for the past four weeks by parent interview;

1. ≥ 30 minutes delayed sleep onset, ≥ 3 times per week

2. Sleep association problems, ≥ 3 nights per week, child falls asleep in a
location other than his/her bed and requires parental intervention to return to
his/her bed

3. Nighttime Awakenings, ≥ 3 times per week, and child disturbs parent or enters
into the parents' bedroom.

4. Early Morning Awakenings, before 5 am ≥ 3 times per week and the child disturbs
family members

- CGI Severity rating of ≥ 4 (Moderate) by the independent evaluator for sleep onset
and/or sleep maintenance disruption at BL 2;

- care provider who can reliably bring subject to clinic visits and provide trustworthy
ratings;

- stable dose of psychotropic medications (for at least 4 weeks with no plans to change
over the course of the study);

- anticonvulsant if used for mood lability and it is working well;

- stable dose of exogenous melatonin for at least 4 weeks with no plans to change over
the course of the study, as long as Phase II eligibility criteria are met prior to
enrollment;

- sleep hygiene education responders who have relapsed and meet the Phase II study
eligibility criteria

Exclusion Criteria:

- DSM-V diagnosis of bipolar disorder;

- subjects who are either melatonin naïve or who have not had an adequate trial of
exogenous melatonin (defined as 3-5 mg for ≥ 4 weeks);

- seizure disorder/epilepsy;

- significant physical illness (e.g., serious cardiovascular, liver or renal
pathology);

- medications specifically given for insomnia;

- pregnancy or sexually-active females without birth control;

- taking supplements or other complementary medical treatments where dose cannot be
held at current level for duration of study;

- weight less than 15 kg;

- use of medicines for physical ailments that might interact with CLN or TRZ, such as
guanfacine (Tenex, Intuniv), and propranolol (Inderol) or extended release clonidine
(Kapvay);

- allergy to CLN or TRZ;

- Sleep Disordered Breathing (SDB) as defined by a total score of ≥ 3 on the CSHQ SDB
subscale and parent report;

- prior adequate trial of CLN for sleep disturbance defined as at least 0.2mg q hs for
1 week;

- prior adequate trial of TRZ for sleep disturbance defined as ≥ 50 mg/day for 1 week;

- hyperthyroidism