Clinical trial NCT02812368 (phase 2, status: withdrawn)
Conditions: autism spectrum disorder
ICD codes: Z16.12
Drugs: clonidine, placebo (for clonidine)
SMILES: ClC1=CC=CC(Cl)=C1NC1=NCCN1, CN1C(=O)C=C(N2CCC[C@@H](N)C2)N(CC2=C(C=CC=C2)C#N)C1=O
Reason stopped: 
    failure to recruit
  
Eligibility 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;

               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