Efficacy and Safety of Circadin® in the Treatment of Sleep Disturbances in Children With Neurodevelopment Disabilities

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2013 by Neurim Pharmaceuticals Ltd.
Sponsor:
Information provided by (Responsible Party):
Neurim Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier:
NCT01906866
First received: July 11, 2013
Last updated: March 4, 2015
Last verified: July 2013
  Purpose

The purpose of this study is to establish the efficacy and safety of Circadin in children with neurodevelopmental disorders and to determine the dose, this randomized, placebo-controlled study is planned to evaluate the efficacy of a double-blind, 13 week treatment period with Circadin 2/5mg in improving maintenance of sleep, sleep latency and additional parameters in children with neurodevelopmental disabilities. The efficacy and safety of Circadin 2/5 mg will continue to be assessed during an open-label extension period of 13 weeks.


Condition Intervention Phase
Sleep Disorders
Drug: Circadin 2/5/10 mg
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: A Randomized, Placebo-controlled Study to Investigate the Efficacy and Safety of Circadin® to Alleviate Sleep Disturbances in Children With Neurodevelopmental Disabilities

Resource links provided by NLM:


Further study details as provided by Neurim Pharmaceuticals Ltd.:

Primary Outcome Measures:
  • The total sleep time will be measured for the Circadin 2/5 mg and placebo by a Sleep and nap diary questionnaire after the 13 week, double-blind treatment period. [ Time Frame: up to 1.5 years ] [ Designated as safety issue: No ]
    Questionnaire


Secondary Outcome Measures:
  • Sleep latency will be measured for the Circadin 2/5 mg and placebo by a Sleep and Nap Diary after 13 weeks of double-blind treatment. [ Time Frame: up to 1.5 years ] [ Designated as safety issue: No ]
    questionnaire

  • The duration of wake after sleep onset period will be measured for the Circadin 2/5 mg and placebo by a Sleep and Nap Diary after 13 weeks of double-blind treatment. [ Time Frame: up to 1.5 years ] [ Designated as safety issue: No ]
    Questionnaire

  • The number of awakenings during the night will be measured for the Circadin 2/5 mg and placebo by a Sleep and Nap Diary after 13 weeks of double-blind treatment. [ Time Frame: up to 1.5 years ] [ Designated as safety issue: No ]
    Questionnaire

  • The duration of the longest sleep period will be measured for the Circadin 2/5 mg and placebo by a Sleep and Nap Diary after 13 weeks of double-blind treatment. [ Time Frame: up to 1.5 Years ] [ Designated as safety issue: No ]
    Questionnaire

  • The children's social functioning at home, in school, and community settings will be measured for the Circadin 2/5 mg and placebo by the Children Global Assessment Scale (CGAS) Questionnaire after 13 weeks of double-blind treatment. [ Time Frame: up to 1.5 years ] [ Designated as safety issue: No ]
    Questionnaire

  • The children's behavior at home, in school, and community will be measured for the Circadin 2/5 mg and placebo by the Strength of Difficulties Questionnaire (SDQ) Questionnaire filled out by the parents after 13 weeks of double-blind treatment. [ Time Frame: up to 1.5 years ] [ Designated as safety issue: No ]
    Questionnaire

  • The number of dropouts between Circadin 2/5 mg to that of placebo will be compared during the 13 weeks of double-blind treatment. [ Time Frame: up to 1.5 years ] [ Designated as safety issue: No ]
  • Sleep parameters (rest/activity cycles) will be measured for the Circadin 2/5 mg and placebo as measured by actigraphy after 13 weeks of double-blind treatment. [ Time Frame: up to 1.5 years ] [ Designated as safety issue: No ]
    The Actigraph will be worn on the wrist at night and collect the Sleep parameters

  • Safety and tolerability throughout the study will be measured for the Circadin 2/5 mg and placebo throughout the study using AE eliciting method Treatment Emergent Signs and Symptoms (TESS) [ Time Frame: up to 2.5 years ] [ Designated as safety issue: Yes ]
    Questionnaire

  • The following Vital Signs will be measured: blood pressure, pulse, breathing and body temperature. They will be compared between the Circadin and placebo groups. [ Time Frame: up to 2.5 years ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 120
Study Start Date: October 2013
Estimated Study Completion Date: December 2017
Estimated Primary Completion Date: August 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Circadin 2/5/10 mg Drug: Circadin 2/5/10 mg
Active arm
Placebo Comparator: Placebo
Placebo arm
Drug: Placebo

  Eligibility

Ages Eligible for Study:   2 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Must be children 2 to 17.5 years of age at Visit 2 who comply with taking the study drug.
  2. Must have written informed consent provided by a legal guardian and assent (if needed).
  3. Must have a documented history of ASD according to ICD-10 or DSM-5 or neurodevelopmental disabilities caused by neurogenetic diseases (Smith-Magenis syndrome [SMS], Angelman syndrome, Bourneville's disease [tuberous sclerosis]) as confirmed by case note review showing that diagnosis was reached through assessment by a community paediatrician or paediatric neurologist, who took into account early developmental history and school records.
  4. Must have current sleep problems including: A minimum of 3 months of impaired sleep defined as <6 hours of continuous sleep with more than 0.5 hour sleep latency from light off in 3 out of 5 nights.
  5. Must be on a stable dose of non-excluded medication for 3 months, including anti-epileptics, anti-depressants (SSRIs), stimulants, all mood changing drugs and beta blockers.
  6. The sleep disturbance is not due to the direct physiological effects of the medication (SSRIs, stimulants, etc.).

At the end of 4 weeks of sleep hygiene training and 2 weeks of run-in, children will be eligible to continue the study if they comply with the following:

  1. Continue to fulfil sleep problem criteria (see Inclusion Criterion 4).
  2. Parents demonstrate compliance in Sleep and Nap Diary completion (5 out of 7 nights).
  3. Continue to fulfil all other eligibility criteria.

Exclusion Criteria:

  1. Have had treatment with any form of melatonin within 2 weeks prior to Visit 1.
  2. Have a known allergy to melatonin or lactose.
  3. Have a known moderate to severe sleep apnea.
  4. Have untreated medical/ineffectively treated/psychological condition that may be the etiology of sleep disturbances.
  5. Did not respond to previous Circadin therapy based on past medical history records in the last 2 years.
  6. Are taking or have been taking disallowed medication within 2 weeks prior to Visit 1.
  7. Are females of child bearing potential that are not using contraceptives.
  8. Are currently participating in a clinical trial or have participated in a clinical trial involving medicinal product within the last 3 months prior to the study.

    -

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01906866

Contacts
Contact: Neurim Pharmaceutical (1991) Ltd. +972-3-6499340 neurim@neurim.com

Locations
United States, Arizona
Southwest Autism Research and Resource Center (SARRC) Recruiting
Phoenix, Arizona, United States
Contact: Sharman Ober-Reynolds    602-218-8133 ext 1011    SOberReynolds@autismcenter.org   
Contact: Ericka Mullinex       emullinix@autismcenter.org   
Principal Investigator: Raun Melmed, MD         
United States, Colorado
Deltawaves Sleep Disorder and Research Center Recruiting
Colorado Springs, Colorado, United States
Contact: Karen Schardin    719-262-9283    Karen@deltawaves.org   
Principal Investigator: Kent Roberson, MD         
United States, Florida
Crystal BioMedical Research, LLC Recruiting
Miami Lakes, Florida, United States, 33014
Contact: Gabriela Gonzalez    305-828-7900    Gmanager@CrystalBiomedicalResearch.com   
Contact: Mailyn Perez    305-828-7900    mperez@crystalbiomedicalresearch.com   
Principal Investigator: Angel Ernesto Rico, MD         
Lake Mary Pediatrics Recruiting
Orange City, Florida, United States
Contact: Heidi Andersen, RN    386-960-8282    lmpresearch2@gmail.com   
Principal Investigator: Karen Hillock, MD         
Mate Lazlo Recruiting
West Palm Beach, Florida, United States
Contact: Katrina Morgan    561-626-5551    study.drmate@gmail.com   
Principal Investigator: Laszlo Mate, MD         
United States, Maryland
Kennedy Krieger Institute Recruiting
Baltimore, Maryland, United States, 21205
Contact: Gary Saum, MPH    443-923-3850    Saum@kennedykrieger.org   
Principal Investigator: Robert Findling         
United States, Nevada
Child Neurology Specialists/ CRCN Recruiting
Henderson, Nevada, United States, 89052
Contact: Darlene Steljes    702-893-8968    dsteljes@crcnnv.com   
Principal Investigator: Roshan Raja, MD         
United States, Pennsylvania
The children`s hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States
Contact: Wu Eileen    215-590-4470    ChorneyL@email.chop.edu   
Contact: Lauren Vernau    267-426-2586    VERNAUL@EMAIL.CHOP.EDU   
Principal Investigator: Amanda Bennet, Dr         
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States
Contact: diane fawkes    615-936-0342    diane.fawkes@vanderbilt.edu   
Principal Investigator: Beth Malow, MD         
United States, Texas
INSITE Clinical Research Recruiting
Desoto, Texas, United States, 75115
Contact: Lynda Nelson    972-707-9640    lnelson@shiwachmdpa.com   
Principal Investigator: Rajinder Shiwach, MD         
Red Oak Psychiatry Associates Recruiting
Houston, Texas, United States
Contact: Elissa Molloy-Plaza    281-893-4111 ext 155    ropa7@earthlink.net   
Contact: Julie Brekke       ropa20@redoakpsychiatry.com   
Principal Investigator: Lawrence Ginsberg, MD         
Sleep Therapy & Research Center Recruiting
San Antonio, Texas, United States
Contact: Sue Rafati    210-931-3318    rafati.sue@sleeptrc.com   
Principal Investigator: Nagwa Lamaie, MD         
United States, Utah
Ericksen Research & Development Recruiting
Clinton, Utah, United States, 32763
Contact: Madison Kenley, BS    801-614-5520    madison@westsidemedical.org   
Principal Investigator: Samantha Bostrom, MD         
Finland
Helsinki Sleep Clinic Vitalmed OY Recruiting
Helsinki, Finland
Contact: Minna Kuurne    0035 8102311488    minna.kuurne-koivisto@vitalmed.fi   
Principal Investigator: Partinen         
France
Hospital Raymond Poincare Recruiting
Garches, France
Contact: Jean-Marc Pinard    +33-1-47107930    jean-marc.pinard@rpc.aphp.fr   
Principal Investigator: Jean-Marc Pinard, Dr         
Strasbourg University Hospital Depatment of Child Psychiatry & Neurology Recruiting
Strasbourg,, France
Contact: Camille Scmidt    0033 388115078    Schroder-Camille Scmidt <camille.schmidt@chru-strasbourg.fr>   
Principal Investigator: Carmen Schroder         
Netherlands
Yulius Mental Health Organization Recruiting
Barendrecht/ Dordercht, Netherlands
Contact: D.Bastiaansen    0031 88 4056956    D.Bastiaansen@yulius.nl   
Principal Investigator: Athanasios Maras         
University Medical Center Groningen Recruiting
Groningen, Netherlands
Contact    0031 503681100    p.hoekstra@accare.nl   
Principal Investigator: Pieter Hoekstra         
United Kingdom
Blackpool Victoria Teaching Hospitals NHS Foundation Trust Recruiting
Blackpool, United Kingdom
Contact: Jacqueline Bradley    0044 1253(95)1522    Jacqueline.Bradley@bfwhospitals.nhs.uk   
Principal Investigator: Megan Thomas         
Guy's & St. Thomas's NHS Foundation Trust of St Thomas's Hospital Recruiting
London, United Kingdom
Contact: katherine blackstone    020 7188 7188    katherine.blackstone@gstt.nhs.uk   
Principal Investigator: Paul Gringras, MD         
University Hospital Southampton NHS Foundation Trust Recruiting
Southampton, United Kingdom
Contact: Danny Pratt,    0044 2381206322    Danny.Pratt@uhs.nhs.uk   
Principal Investigator: Catherine Hill         
Sponsors and Collaborators
Neurim Pharmaceuticals Ltd.
Investigators
Principal Investigator: Paul Gringras, PhD Thoma`s Hospital, Westminster Bridge Rd, London
Principal Investigator: Robert Findling, MD Kennedy Krieger Institute, Baltimore, Maryland, USA
  More Information

No publications provided

Responsible Party: Neurim Pharmaceuticals Ltd.
ClinicalTrials.gov Identifier: NCT01906866     History of Changes
Other Study ID Numbers: NEU_CH_7911
Study First Received: July 11, 2013
Last Updated: March 4, 2015
Health Authority: United States: Food and Drug Administration

Keywords provided by Neurim Pharmaceuticals Ltd.:
Sleep disturbance
Circadian
Prolong release melatonin
Autism Spectrum Disorder
Smith-Magenis Syndrome
Angelman Syndrome
tuberous sclerosis

Additional relevant MeSH terms:
Parasomnias
Sleep Disorders
Dyssomnias
Mental Disorders
Nervous System Diseases
Neurologic Manifestations
Signs and Symptoms
Melatonin
Antioxidants
Central Nervous System Agents
Central Nervous System Depressants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on May 21, 2015