Metoclopramide as Treatment of Clozapine-induced Hypersalivation

NCT02222220 | Completed Phase 3

• 1 other identifier: VLAK-14
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

Brief Summary

Hypersalivation (sialorrhea or ptyalism) is known as a frequent, disturbing, uncomfortable adverse effect of clozapine therapy that can lead to noncompliance. Until now there is no effective enough treatment for this side effect. Previous studies demonstrated that different medications from the substitute benzamide derivatives group: amisulpride, sulpiride (higher selective binding to the D2/D3 dopamine receptor) and moclobemide (reversible inhibitor of monoamine oxidase A, which inhibits the deamination of serotonin, norepinephrine and dopamine) may be effective as a treatment of clozapine-induced hypersalivation (CIH). Moreover, there is another substitute benzamide derivative: metoclopramide (dopamine D2 antagonist, usually used as antiemetic medication in general medicine). The investigators hypothesis assumes that anti-salivation effect characterizes the whole group of benzamide. The aim of this study was to examine the efficacy of metoclopramide as an optional possibility for management of CIH.

Conditions

Clozapine-induced Hypersalivation

Outcome Measures

Primary Outcomes (1)

• Nocturnal Hypersalivation Rating Scale (NHRS)

  every week, up to 4 weeks

Secondary Outcomes (1)

• Drooling Severity Scale (DSS)

  every week, up to 4 weeks

Other Outcomes (1)

• The Positive and Negative Syndrome Scale (PANSS)

  every week, up to 4 weeks

Study Arms (2)

metoclopramide

PLACEBO COMPARATOR

61 participating subjects were randomized into 2 groups: 30 received metoclopramide up to 30 mg/day and 31 received placebo, each for 4 weeks in a double-blind mode

Drug: Metoclopramide; Drug: placebo

metocliopramide

EXPERIMENTAL

61 participating subjects were randomized into 2 groups: 30 received metoclopramide up to 30 mg/day and 31 received placebo, each for 4 weeks in a double-blind mode

Drug: Metoclopramide; Drug: placebo

Interventions

Metoclopramide DRUG

30 mg/day during 4 weeks

metocliopramide; metoclopramide

placebo DRUG

metocliopramide; metoclopramide

Eligibility Criteria

• Age: 19 Years - 57 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age 18-60 years, male or female
• DSM-IV criteria for schizophrenia
• Clozapine treatment
• At least score \>2 on the Nocturnal Hypersalivation Rating Scale (NHRS)

You may not qualify if:

• Evidence of organic brain damage, mental retardation, alcohol or drug abuse
• Patients suffering from pheochromocytoma
• Patients suffering from Parkinson's disease

Sponsors & Collaborators

• Beersheva Mental Health Center: lead
• Tirat Carmel Mental Health Center: collaborator

Study Sites (1)

Be'er Sheva Mental Health Center,

Beersheba, 8417000, Israel

Location

Related Publications (2)

• Safferman A, Lieberman JA, Kane JM, Szymanski S, Kinon B. Update on the clinical efficacy and side effects of clozapine. Schizophr Bull 1991;17:247-261. Kaplan & Sadock's Comprehensive Textbook of Psychiatry. Philadelphia: Lippincot Williams & Wilkins, 2005. Baldessarini RJ, Huston-Lyons D, Campbell A, Marsh E, Cohen BM. Do central antiadrenergic actions contribute to the atypical properties of clozapine? Br J Psychiatry Suppl 1992:12-16. Kreinin A, Epshtein S, Sheinkman A, Tell E. Sulpiride addition for the treatment of clozapine-induced hypersalivation: preliminary study. Isr J Psychiatry Relat Sci 2005;42:61-63. Kreinin A, Novitski D, Weizman A. Amisulpride treatment of clozapine-induced hypersalivation in schizophrenia patients: a randomized, double-blind, placebo-controlled cross-over study. Int Clin Psychopharmacol 2006;21:99-103. Kreinin A, Miodownik C, Libov I, Shestakova D, Lerner V. Moclobemide treatment of clozapine-induced hypersalivation: pilot open study. Clin Neuropharmacol 2009;32:151-153. Justin-Besancon L, Laville C. [Antiemetic Action of Metoclopramide with Respect to Apomorphine and Hydergine]. C R Seances Soc Biol Fil 1964;158:723-727. Rang HP, Dale MM, Ritter JM, Moore PK. Pharmacology. 5th ed. Edinburgh: Churchill Livingstone; 2003. Sweetman S, editor. Martindale: The complete drug reference. 34th ed. London: Pharmaceutical Press; 2004. Tonini M, Candura SM, Messori E, Rizzi CA. Therapeutic potential of drugs with mixed 5-HT4 agonist/5-HT3 antagonist action in the control of emesis. Pharmacol Res 1995;31:257-260. Kay SR, Fiszbein A, Opler LA. The positive and negative syndrome scale (PANSS) for schizophrenia. Schizophr Bull 1987;13:261-276. Chouinard G, Ross-Chouinard A, Annable L, Jones B. Extrapyramidal Symptom Rating Scale. Can J Neurol Sci (abstract) 1980;7:233.

  BACKGROUND

• Kreinin A, Miodownik C, Mirkin V, Gaiduk Y, Yankovsky Y, Bersudsky Y, Lerner PP, Bergman J, Lerner V. Double-Blind, Randomized, Placebo-Controlled Trial of Metoclopramide for Hypersalivation Associated With Clozapine. J Clin Psychopharmacol. 2016 Jun;36(3):200-5. doi: 10.1097/JCP.0000000000000493.

  PMID: 27028980 DERIVED

MeSH Terms

Interventions

Metoclopramide

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; para-Aminobenzoates; Aminobenzoates; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Chlorobenzoates; Hydroxybenzoate Ethers; Hydroxybenzoates; Hydroxy Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenyl Ethers; Phenols

Study Officials

• Vladimir Lerner, MD, PhD

  Ben-Gurion University of the Negev

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Vladimir Lerner

Study Record Dates

• First Submitted: August 17, 2014
• First Posted: August 21, 2014
• Study Start: January 1, 2012
• Primary Completion: May 1, 2014
• Study Completion: May 1, 2014
• Last Updated: August 21, 2014

Record last verified: 2012-01

Locations

IL (1)