Study of add-on Ramelteon Therapy on Sleep and Circadian Rhythm Disruption in Patients With Schizophrenia

NCT03075657 | Completed Phase 4

• 1 other identifier: T/IM-NF/Pharma/01/17
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed study has been planned to evaluate the effect of add-on ramelteon on sleep pattern/quality and circadian rhythm disruption in patients with schizophrenia.

Conditions

Schizophrenia

Outcome Measures

Primary Outcomes (1)

• Change in serum melatonin over 4 weeks from baseline

  ELISA

  Baseline and 4 weeks

Secondary Outcomes (4)

• Change in quality of sleep over 4 weeks from baseline

  Baseline and 4 weeks

• Change in urinary melatonin(6MTs) over 4 weeks from baseline

  Baseline and 4 weeks

• Change in serum AANAT enzyme over 4 weeks from baseline

  Baseline and 4 weeks

• Change in severity of symptoms of schizophrenia over 4 weeks from baseline

  Baseline and 4 weeks

Study Arms (4)

Risperidone group

ACTIVE COMPARATOR

Schizophrenia patients with predominant negative symptoms on Risperidone monotherapy

Drug: Risperidone

Risperidone with Ramelteon group

EXPERIMENTAL

Schizophrenia patients with predominant negative symptoms on Risperidone with add-on Ramelteon therapy

Drug: Risperidone and Ramelteon

Haloperidol group

ACTIVE COMPARATOR

Schizophrenia patients with predominant positive symptoms on Haloperidol monotherapy

Drug: Haloperidol

Haloperidol with Ramelteon group

EXPERIMENTAL

Schizophrenia patients with predominant positive symptoms on Haloperidol with add-on Ramelteon therapy

Drug: Haloperidol and Ramelteon

Interventions

Risperidone DRUG

Risperidone will be prescribed at dose of 2 mg per day

Risperidone group

Risperidone and Ramelteon DRUG

Ramelteon will be prescribed 8mg/day as an add-on therapy to Risperidone 2 mg per day

Risperidone with Ramelteon group

Haloperidol DRUG

Haloperidol will be prescribed at a dose of 4 mg per day

Haloperidol group

Haloperidol and Ramelteon DRUG

Ramelteon will be prescribed 8mg/day as an add-on therapy to Haloperidol 4 mg per day

Haloperidol with Ramelteon group

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• All adult patients of either sex with age range 18-65 years with the clinical diagnosis of schizophrenia. (DSM-V)
• Legal guardian of patients consenting to participate in the study by signing the informed consent form.

You may not qualify if:

• Schizoaffective disorder or schizophrenia with somatoform disorders.
• Highly agitated patients who need immediate treatment.
• Patients who are already under treatment for the presenting conditions.
• Patients with comorbid substance abuse or history of organicity
• Patients with known history of dementia, obstructive sleep apnoea syndrome, diabetes mellitus.
• Pregnant and nursing women.
• History of allergy or hypersensitivity to ramelteon.
• Legal guardian of patients not willing to participate in the study.

Sponsors & Collaborators

• All India Institute of Medical Sciences, Bhubaneswar: lead

Study Sites (1)

All India Institute of Medical Sciences (AIIMS)

Bhubaneswar, Odisha, 751019, India

Location

Related Publications (18)

• Cohrs S. Sleep disturbances in patients with schizophrenia : impact and effect of antipsychotics. CNS Drugs. 2008;22(11):939-62. doi: 10.2165/00023210-200822110-00004.

  PMID: 18840034 RESULT

• Wehr TA, Aeschbach D, Duncan WC Jr. Evidence for a biological dawn and dusk in the human circadian timing system. J Physiol. 2001 Sep 15;535(Pt 3):937-51. doi: 10.1111/j.1469-7793.2001.t01-1-00937.x.

  PMID: 11559786 RESULT

• Afonso P, Figueira ML, Paiva T. Sleep-promoting action of the endogenous melatonin in schizophrenia compared to healthy controls. Int J Psychiatry Clin Pract. 2011 Nov;15(4):311-5. doi: 10.3109/13651501.2011.605954. Epub 2011 Aug 28.

  PMID: 22122006 RESULT

• Wulff K, Dijk DJ, Middleton B, Foster RG, Joyce EM. Sleep and circadian rhythm disruption in schizophrenia. Br J Psychiatry. 2012 Apr;200(4):308-16. doi: 10.1192/bjp.bp.111.096321. Epub 2011 Dec 22.

  PMID: 22194182 RESULT

• Mann K, Rossbach W, Muller MJ, Muller-Siecheneder F, Pott T, Linde I, Dittmann RW, Hiemke C. Nocturnal hormone profiles in patients with schizophrenia treated with olanzapine. Psychoneuroendocrinology. 2006 Feb;31(2):256-64. doi: 10.1016/j.psyneuen.2005.08.005. Epub 2005 Sep 26.

  PMID: 16185814 RESULT

• Cohrs S, Pohlmann K, Guan Z, Jordan W, Meier A, Huether G, Ruther E, Rodenbeck A. Quetiapine reduces nocturnal urinary cortisol excretion in healthy subjects. Psychopharmacology (Berl). 2004 Jul;174(3):414-20. doi: 10.1007/s00213-003-1766-6. Epub 2004 Jan 20.

  PMID: 14735295 RESULT

• Robinson S, Rosca P, Durst R, Shai U, Ghinea C, Schmidt U, Nir I. Serum melatonin levels in schizophrenic and schizoaffective hospitalized patients. Acta Psychiatr Scand. 1991 Sep;84(3):221-4. doi: 10.1111/j.1600-0447.1991.tb03133.x.

  PMID: 1950621 RESULT

• Monteleone P, Natale M, La Rocca A, Maj M. Decreased nocturnal secretion of melatonin in drug-free schizophrenics: no change after subchronic treatment with antipsychotics. Neuropsychobiology. 1997;36(4):159-63. doi: 10.1159/000119377.

  PMID: 9396013 RESULT

• Hajak G, Rodenbeck A, Bandelow B, Friedrichs S, Huether G, Ruther E. Nocturnal plasma melatonin levels after flunitrazepam administration in healthy subjects. Eur Neuropsychopharmacol. 1996 May;6(2):149-53. doi: 10.1016/0924-977x(96)00005-3.

  PMID: 8791041 RESULT

• Kabuto M, Namura I, Saitoh Y. Nocturnal enhancement of plasma melatonin could be suppressed by benzodiazepines in humans. Endocrinol Jpn. 1986 Jun;33(3):405-14. doi: 10.1507/endocrj1954.33.405.

  PMID: 3757924 RESULT

• 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: 21975110 RESULT

• Lavie P. Melatonin: role in gating nocturnal rise in sleep propensity. J Biol Rhythms. 1997 Dec;12(6):657-65. doi: 10.1177/074873049701200622.

  PMID: 9406042 RESULT

• 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: 17335321 RESULT

• Miyamoto M. Pharmacology of ramelteon, a selective MT1/MT2 receptor agonist: a novel therapeutic drug for sleep disorders. CNS Neurosci Ther. 2009 Winter;15(1):32-51. doi: 10.1111/j.1755-5949.2008.00066.x.

  PMID: 19228178 RESULT

• Johnson MW, Suess PE, Griffiths RR. Ramelteon: a novel hypnotic lacking abuse liability and sedative adverse effects. Arch Gen Psychiatry. 2006 Oct;63(10):1149-57. doi: 10.1001/archpsyc.63.10.1149.

  PMID: 17015817 RESULT

• Spadoni G, Bedini A, Lucarini S, Mor M, Rivara S. Pharmacokinetic and pharmacodynamic evaluation of ramelteon : an insomnia therapy. Expert Opin Drug Metab Toxicol. 2015 Jul;11(7):1145-56. doi: 10.1517/17425255.2015.1045487. Epub 2015 May 8.

  PMID: 25956235 RESULT

• Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull. 1987;13(2):261-76. doi: 10.1093/schbul/13.2.261.

  PMID: 3616518 RESULT

• Buysse DJ, Reynolds CF 3rd, Monk TH, Berman SR, Kupfer DJ. The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research. Psychiatry Res. 1989 May;28(2):193-213. doi: 10.1016/0165-1781(89)90047-4.

  PMID: 2748771 RESULT

MeSH Terms

Conditions

Schizophrenia

Interventions

Risperidone; ramelteon; Haloperidol

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Butyrophenones; Ketones; Organic Chemicals

Study Officials

• DEBASISH HOTA, DM

  AIIMS, BHUBANESWAR

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The rating of PANSS and PSQI will be done by one Psychiatrist who will be blind to the groups and treatment alloted.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: March 6, 2017
• First Posted: March 9, 2017
• Study Start: May 1, 2017
• Primary Completion: June 15, 2018
• Study Completion: August 31, 2018
• Last Updated: May 3, 2019

Record last verified: 2019-05

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)