Developing New Treatments for Tourette Syndrome: Therapeutic Trials With Modulators of Glutamatergic Neurotransmission
Status:
Completed
Trial end date:
2013-09-01
Target enrollment:
Participant gender:
Summary
A joint NIH -Tourette Syndrome Association Conference has emphasized the critical need for
the testing and development of new pharmacotherapy for tic suppression in Tourette syndrome
(TS). This submission is a safety, tolerability and efficacy pilot study using two
medications that modulate glutamate neurotransmission, riluzole, a glutamate antagonist, and
D-serine, a glutamate agonist. Glutamate is the primary excitatory neurotransmitter in the
central nervous system, an essential component of pathways implicated in TS and an extensive
modulator of dopamine, the major neurotransmitter associated with tics.
This is a single site, short-term, proof of concept study of riluzole and D-serine for the
treatment of tics. Each medication will be evaluated and compared to placebo as part of a
double-blind, randomized, parallel, flexible dose, three-arm, 8-week, treatment protocol
(D-serine, riluzole, or placebo). A total of sixty patients (age 8-17 years) with TS and
moderate to moderately-severe tics will receive study medication according to a 2:1 (dopamine
modulating drug: placebo), randomized schedule, i.e., riluzole (n=24), D-serine (n=24),
placebo (n=12). The primary outcome measure is tic suppression as determined by changes in
the Total Tic Subscore of the Yale Global Tic Severity Scale (YGTSS). Secondary tic outcome
measures include changes in the YGTSS Total Score and two Global Impression Scales. Further,
since both riluzole and D-serine have been proposed as treatments for obsessive-compulsive
behaviors, a TS co-morbidity, these symptoms will be followed. Safety measures include serial
physical examinations, vital signs, laboratory studies (comprehensive metabolic panel,
complete blood count, plasma amino acids, and urine analyses), documentation of side effects
and adverse events, and measurement of changes in ADHD, depression and anxiety.
This pilot investigation will provide important proof-of-concept data on glutamate therapies
for TS and, in turn, evidence for large-scale, multi-center clinical trials.