Efficacy and Safety of Circadin for Non-24 Hour Sleep-Wake Disorder in Totally Blind Subjects

A Double-Blind, Placebo-Controlled Study of Circadin™ for Non-24 Hour Sleep-Wake Disorder in Totally Blind Subjects

The aim of this placebo-controlled randomized study was to evaluate the efficacy of Circadin™ 2 mg in improving total night sleep duration and stabilizing the circadian clock phase in totally blind subjects with non-24 hour sleep-wake disorder.

Study Overview

• Status: Completed
• Conditions: Blindness; Non-24 Hour Sleep-Wake Disorder
• Intervention / Treatment: Drug: melatonin (Circadin); Drug: placebo

Detailed Description

This was a multi-center, double-blind, placebo-controlled study of a once-daily (QD) dose of Circadin™ 2 mg in subjects with non-24 hour sleep-wake disorder. Subjects were initially treated with placebo for 2 weeks and then were randomly assigned in a 1:1 ratio to receive Circadin™ 2 mg or placebo for 6 weeks, followed by a 2-week washout period. The primary objective was to assess the effect of Circadin 2 mg given once daily for 6 weeks on total night sleep duration. Secondary objectives were other sleep variables recorded by the diary like sleep latency, daytime naps and sleep offset time. Other endpoints were CGIC score for Severity of Illness and Global Improvement and WHO (Five) Well-Being Index score.

• Study Type: Interventional
• Enrollment (Actual): 13
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30382
      • Sleep Disorders Center of Atlanta
  • New York
    • New York, New York, United States, 10019
      • Clinlabs, Inc.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female subjects aged 20-80, having no conscious perception of light.
• Meeting the criteria for diagnosing Non-24h cycle in the clinical setting: 1) difficulty initiating sleep or difficulty in awakening, 2) progressive delay of sleep phase with inability to maintain entrainment to 24-hour-day, and 3) presence of the sleep pattern for at least six weeks.
• Average total night sleep duration of less than 6 hours per night for at least six weeks.
• Ability to ingest oral medication and participate in all scheduled evaluations.
• Signing of the Informed Consent approved by the Ethics Committee. The Informed Consent will be written in both Braille and black-and-white forms for blind subject and sighted witness.
• Education or a work history sufficient to exclude mental retardation.
• Stable medications for non-excluded concurrent medical conditions for four weeks prior to the screening visit.

Exclusion Criteria:

• Presence of medical disorders other than those related to blindness and medical treatment that may influence melatonin production, sleep or alertness. To be ascertained by medical history, complete physical examination including ECG and general biochemical work-up including complete blood count, serum chemistries, and urine analysis.
• Presence of a psychiatric or mental disorder to be assessed by a structured psychiatric interview performed by a trained individual.
• History of seizure disorders.
• Irregular lifestyle or life pattern (e.g. shift workers and patients unable to keep the study routine).
• Presence of a sleep problem revealed that may explain the subjects' complaints, such as sleep disordered breathing, restless leg syndrome or periodic limb movement syndrome.
• Use of benzodiazepines or other hypnotics during the study and preceding two weeks or 5 half lives whichever is longer.
• Known or suspected hypersensitivity to exogenous melatonin or melatonin receptor agonists
• Use of melatonin during preceding two weeks
• Use of psychiatric medications during the study and preceding three months.
• History of autoimmune diseases
• Pharmacological immuno-suppression.
• Pregnancy or lactation, child-bearing potential with a lack of adequate contraception.
• History of severe pathology likely to recur during or immediately after the study.
• Participation in a clinical trial with any investigational agent within two months prior to study enrollment.
• Patients incapable of performing the daily call to the study IVRS system and reporting on the questionnaires.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: placebo; one tablet per day 2 hours before going to bed
Experimental: Circadin; Circadin is 2 mg of prolonged release melatonin	Drug: melatonin (Circadin); 2 mg prolonged release melatonin tablets once daily 2 hours before going to bed; Other Names: Circadin; ATC code N05CH01

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Total sleep time	six weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Daily diary records of sleep latency, sleep maintenance , total duration of naps;	six weeks

Collaborators and Investigators

• Sponsor: Neurim Pharmaceuticals Ltd.
• Investigators: Principal Investigator: Alan Lankford, PhD, Sleep Disorders Center of Atlanta; Principal Investigator: Gary Zammit, PhD, Clinlabs, Inc.

Publications and helpful links

General Publications

• Roth T, Nir T, Zisapel N. Prolonged release melatonin for improving sleep in totally blind subjects: a pilot placebo-controlled multicenter trial. Nat Sci Sleep. 2015 Jan 29;7:13-23. doi: 10.2147/NSS.S71838. eCollection 2015.

Study record dates

Study Major Dates

• Study Start: February 1, 2006
• Primary Completion (Actual): August 1, 2007
• Study Completion (Actual): October 1, 2007

Study Registration Dates

• First Submitted: September 3, 2009
• First Submitted That Met QC Criteria: September 3, 2009
• First Posted (Estimate): September 4, 2009

Study Record Updates

• Last Update Posted (Estimate): September 9, 2009
• Last Update Submitted That Met QC Criteria: September 6, 2009
• Last Verified: September 1, 2009

More Information

Terms related to this study

• Keywords: totally blind subjects
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Dyssomnias; Eye Diseases; Neurologic Manifestations; Occupational Diseases; Sensation Disorders; Vision Disorders; Chronobiology Disorders; Sleep Wake Disorders; Blindness; Sleep Disorders, Circadian Rhythm; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: CIRCADIN 1