Clinical Drug Experience Knowledgebase

Criteria

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;

≥ 30 minutes delayed sleep onset, ≥ 3 times per week
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
Nighttime Awakenings, ≥ 3 times per week, and child disturbs parent or enters into the parents' bedroom.
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