NCT01431092

Brief Summary

In this trial, researchers aim to investigate if prolonged-release melatonin can facilitate the withdrawal of chronic benzodiazepine administration in patients with schizophrenia. Furthermore, researchers will investigate the association of benzodiazepine dose reduction with the following clinically important variables: sleep, psychophysiology, cognition, social function, and quality of life.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
86

participants targeted

Target at P50-P75 for phase_4 schizophrenia

Timeline
Completed

Started Oct 2011

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 31, 2011

Completed
9 days until next milestone

First Posted

Study publicly available on registry

September 9, 2011

Completed
22 days until next milestone

Study Start

First participant enrolled

October 1, 2011

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

June 1, 2014

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

June 1, 2014

Completed
Last Updated

June 6, 2014

Status Verified

June 1, 2014

Enrollment Period

2.7 years

First QC Date

August 31, 2011

Last Update Submit

June 5, 2014

Conditions

SchizophreniaSchizoaffective DisorderBipolar Affective Disorder

Outcome Measures

Primary Outcomes (1)

  • Benzodiazepine (including benzodiazepine related drugs) dose at 6 months follow-up.

    The general linear model is used with the outcome measure (dose after 6 months) as the dependent variable and the indicator of intervention and the baseline value as the independent variables. If the assumptions of the model cannot be fulfilled either directly or after transformation a non-parametric method will be used.

    6 months follow-up.

Secondary Outcomes (7)

  • Pattern of benzodiazepine dose over time.

    2, 4, and 6 months.

  • The fraction of participants who has completely discontinued benzodiazepines 6 months after initiating trial medication.

    6 months follow-up.

  • Pattern of P300 amplitude (psychophysiology) over time.

    2, 4, and 6 months.

  • Pattern of Brief Assessment of Cognition in Schizophrenia (BACS) composite score over time.

    2, 4, and 6 months.

  • Sleep efficiency (polysomnography) at 6 months follow-up.

    6 months.

  • +2 more secondary outcomes

Study Arms (2)

Melatonin

EXPERIMENTAL
Drug: Melatonin

Placebo

PLACEBO COMPARATOR
Drug: Placebo

Interventions

PlaceboDRUG

Both Circadin and placebo are encapsulated in lactose containing gelatin capsules to optimize the blinding.

Placebo
MelatoninDRUG

Prolonged-release melatonin (Circadin®) 2 mg, once daily, 1-2 hours before bedtime.

Also known as: Prolonged-release melatonin, Circadin®
Melatonin

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age 18+.
  • Written informed consent.

You may not qualify if:

  • Known aggressive or violent behavior.
  • Mental retardation, pervasive developmental disorder, or dementia.
  • Epilepsy, terminal illness, severe comorbidity or unable to understand Danish.
  • Allergic to compounds in the trial medication (melatonin, lactose, starch, gelatin, talc).
  • Hepatic impairment (known diagnosis).
  • Pregnancy and nursing.
  • Missing informed consent.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Center for Neuropsychiatric Schizophrenia Research (CNSR)/Center for Clinical Intervention and Neuropsychiatric Schizophrenia Research (CINS), University of Copenhagen, Mental Health Centre Glostrup, Mental Health Services - Capital Region of Denmark

Glostrup Municipality, 2600, Denmark

Location

Related Publications (8)

  • Volz A, Khorsand V, Gillies D, Leucht S. Benzodiazepines for schizophrenia. Cochrane Database Syst Rev. 2007 Jan 24;(1):CD006391. doi: 10.1002/14651858.CD006391.

    PMID: 17253592BACKGROUND

  • Monti JM, Monti D. Sleep disturbance in schizophrenia. Int Rev Psychiatry. 2005 Aug;17(4):247-53. doi: 10.1080/09540260500104516.

    PMID: 16194796BACKGROUND

  • Buscemi N, Vandermeer B, Hooton N, Pandya R, Tjosvold L, Hartling L, Vohra S, Klassen TP, Baker G. Efficacy and safety of exogenous melatonin for secondary sleep disorders and sleep disorders accompanying sleep restriction: meta-analysis. BMJ. 2006 Feb 18;332(7538):385-93. doi: 10.1136/bmj.38731.532766.F6. Epub 2006 Feb 10.

    PMID: 16473858BACKGROUND

  • Shamir E, Laudon M, Barak Y, Anis Y, Rotenberg V, Elizur A, Zisapel N. Melatonin improves sleep quality of patients with chronic schizophrenia. J Clin Psychiatry. 2000 May;61(5):373-7. doi: 10.4088/jcp.v61n0509.

    PMID: 10847313BACKGROUND

  • Suresh Kumar PN, Andrade C, Bhakta SG, Singh NM. Melatonin in schizophrenic outpatients with insomnia: a double-blind, placebo-controlled study. J Clin Psychiatry. 2007 Feb;68(2):237-41. doi: 10.4088/jcp.v68n0208.

    PMID: 17335321BACKGROUND

  • Garfinkel D, Zisapel N, Wainstein J, Laudon M. Facilitation of benzodiazepine discontinuation by melatonin: a new clinical approach. Arch Intern Med. 1999 Nov 8;159(20):2456-60. doi: 10.1001/archinte.159.20.2456.

    PMID: 10665894BACKGROUND

  • Baandrup L, Fasmer OB, Glenthoj BY, Jennum PJ. Circadian rest-activity rhythms during benzodiazepine tapering covered by melatonin versus placebo add-on: data derived from a randomized clinical trial. BMC Psychiatry. 2016 Oct 13;16(1):348. doi: 10.1186/s12888-016-1062-8.

    PMID: 27737649DERIVED

  • Baandrup L, Fagerlund B, Jennum P, Lublin H, Hansen JL, Winkel P, Gluud C, Oranje B, Glenthoj BY. Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia: a randomized clinical trial - the SMART trial protocol. BMC Psychiatry. 2011 Oct 5;11:160. doi: 10.1186/1471-244X-11-160.

    PMID: 21975110DERIVED

MeSH Terms

Conditions

SchizophreniaPsychotic DisordersBipolar Disorder

Interventions

Melatonin

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic DisordersMental DisordersBipolar and Related DisordersMood Disorders

Intervention Hierarchy (Ancestors)

TryptaminesIndolesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic CompoundsHormonesHormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

  • Lone Baandrup, MD, PhD

    CNSR/CINS

    PRINCIPAL INVESTIGATOR

  • Birte Glenthøj, MD, MSc

    CNSR/CINS

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
MD, Ph.D.

Study Record Dates

First Submitted

August 31, 2011

First Posted

September 9, 2011

Study Start

October 1, 2011

Primary Completion

June 1, 2014

Study Completion

June 1, 2014

Last Updated

June 6, 2014

Record last verified: 2014-06

Locations

DK(1)