Famotidine for Levodopa-induced Dyskinesia in PD

NCT01937078 | Completed Phase 2

• 1 other identifier: MDC FAM 2010
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

Levodopa-induced dyskinesia is a common problem in Parkinson's disease (PD). In particular, targeting non-dopaminergic systems may be an option for reducing dyskinesia without worsening motor symptoms. One such target may be histamine. The central histaminergic system is involved in diverse biological functions including thermoregulation, eating, and sleep; a role in motor activity is suggested by strong histaminergic innervation of the basal ganglia. Histamine H2 receptors are highly expressed in the striatum, particularly on the GABAergic striatal-pallidal and striatal-nigral pathways Histamine H2 stimulation modulates acetylcholine release. Previous studies have demonstrated that blocking acetylcholine with anticholinergic agents can induce chorea. The investigators propose that histamine H2 receptor stimulation decreases acetylcholine in the striatum and increases activity of the direct striatal output pathway, a key component of the neural mechanisms underlying dyskinesia. The investigators hypothesise that H2 antagonists would reduce activity of the direct striatopallidal pathway and so potentially reduce levodopa-induced chorea Famotidine has also been assessed in schizophrenia in a small cases series to treat schizophrenia, with tolerability. Clinical experience thus suggests the suitability of using this agent as a histamine H2 antagonist in clinical studies for PD.

Conditions

Dyskinesia

Outcome Measures

Primary Outcomes (1)

• Change in Dyskinesia severity using Unified Dyskinesia Rating Scale

  on days 1;14;21;35;42;56;63;77

Secondary Outcomes (3)

• Subject-rated dyskinesia severity using Unified Dyskinesia Rating Scale and Lang-Fahn Activities of Daily Living Scale

  on days 1;14;21;35;42;56;63;77

• Parkinsonian disability using UPDRS (blinded investigator-rated

  on days 1;14;21;35;42;56;63;77

• Adverse events

  on days 1;14;21;35;42;56;63;77

Study Arms (1)

active

ACTIVE COMPARATOR

Famotidine will be administered at total daily doses of 80, 120mg, or 160mg per day. Each patient will be randomized to receive each active dose of famotidine (80, 120, or 160mg/d and placebo). Each patient will receive 4 randomized treatment phases - three famotidine (one at each of the dose levels) and one placebo.

Drug: Famotidine

Interventions

Famotidine DRUG

Each patient will receive 4 randomized treatment phases - three famotidine (one at each of the dose levels) and one placebo. Each treatment phase will last for 14 days. Doses of drug will be titrated upwards, starting at 40mg once daily on day one, 40mg twice daily on day two, and 80mg twice daily (or placebo + drug equivalent) from day three and then continue on this dose for the next 12 days. Regardless of treatment phase, subjects will take 2 tablets twice daily, with varying ratios of active famotidine to placebo. Thus famotidine 80mg/d will consist of 1 tablet of 40 mg famotidine plus 1 tablet of placebo twice a day; 120 mg /d famotidine will be 2 tablets at 40 mg morning and 1 tablet famotidine 40 mg plus 1 tablet placebo evening; famotidine 160 mg/d will be famotidine 40 mg tablets, 2 tablets twice a day. The placebo phase will consist of 2 placebo tablets twice a day.

active

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Toronto Western Hospital

Toronto, Ontario, Canada

Location

MeSH Terms

Conditions

Dyskinesias

Interventions

Famotidine

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Susan Fox

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: PI

Study Record Dates

• First Submitted: July 26, 2012
• First Posted: September 9, 2013
• Study Start: April 1, 2011
• Primary Completion: March 1, 2014
• Study Completion: March 1, 2014
• Last Updated: May 5, 2014

Record last verified: 2014-05

Locations

CA (1)