Overview

Famotidine for Levodopa-induced Dyskinesia in PD

Status:
Completed

Trial end date:
2014-03-01

Target enrollment:
0

Participant gender:
All

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.

Phase:

Phase 2

Accepts Healthy Volunteers?

Details

Lead Sponsor:

University Health Network, Toronto

Treatments:

Famotidine
Levodopa

Criteria

Inclusion Criteria:Eligible patients, male and female, will be less than 80 years of age
and be on stable levodopa. Subjects must have stable, bothersome dyskinesia and have an
MDS-UPDRS score 2 or greater, on item 4.2. All anti-parkinsonian medications must be
unchanged for at least one month prior to study enrollment. Subjects may be taking
amantadine at a stable dose for at least one month prior to study onset -

Exclusion Criteria:are prior surgery for PD, Hoehn and Yahr score of 5 when off-medication,
history of moderate to severe renal impairment (creatinine clearance <25 millilitres per
minute, dementia (defined by Montreal Cognitive Scale < 2518 , allergic reaction to
lactose, famotidine or other histamine H2 antagonists

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