A randomized, placebo-controlled trial of latrepirdine in Huntington disease.
OBJECTIVE
To evaluate the safety and tolerability of latrepirdine in Huntington disease (HD) and explore its effects on cognition, behavior, and motor symptoms.


METHODS
Double-blind, randomized, placebo-controlled trial.


METHODS
Multicenter outpatient trial.


METHODS
Ninety-one participants with mild to moderate HD enrolled at 17 US and UK centers from July 18, 2007, through July 16, 2008.


METHODS
Latrepirdine, 20 mg 3 times daily (n = 46), or matching placebo (n = 45) for a 90-day treatment period.


METHODS
The primary outcome variable was tolerability, defined as the ability to complete the study at the assigned drug dosage. Secondary outcome variables included score changes from baseline to day 90 on the Unified Huntington's Disease Rating Scale (UHDRS), the Mini-Mental State Examination (MMSE), and the Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-cog).


RESULTS
Latrepirdine was well tolerated (87% of the patients given latrepirdine completed the study vs 82% in the placebo group), and adverse event rates were comparable in the 2 groups (70% in the latrepirdine group and 80% in the placebo group). Treatment with latrepirdine resulted in improved mean MMSE scores compared with stable performance in the placebo group (treatment effect, 0.97 points; 95% confidence interval, 0.10-1.85; P = .03). No significant treatment effects were seen on the UHDRS or the ADAS-cog.


CONCLUSIONS
Short-term administration of latrepirdine is well tolerated in patients with HD and may have a beneficial effect on cognition. Further investigation of latrepirdine is warranted in this population with HD.
Department of Neurology, University of Virginia, Charlottesville, VA 22908, USA.
Karl
K
Kieburtz
Michael P
MP
McDermott
Tiffini S
TS
Voss
Jody
J
Corey-Bloom
Lisa M
LM
Deuel
E Ray
ER
Dorsey
Stewart
S
Factor
Michael D
MD
Geschwind
Karen
K
Hodgeman
Elise
E
Kayson
Sarah
S
Noonberg
Michael
M
Pourfar
Karen
K
Rabinowitz
Bernard
B
Ravina
Juan
J
Sanchez-Ramos
Lynn
L
Seely
Francis
F
Walker
Andrew
A
Feigin
D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D004311:Double-Blind Method; D004562:Electrocardiography / Q000379:methods; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000188:drug therapy* / Q000503:physiopathology*; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009043:Motor Activity / Q000187:drug effects; D009483:Neuropsychological Tests; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D007211:Indoles; C010119:latrepirdine