A randomized clinical trial of valacyclovir in multiple sclerosis.
OBJECTIVE
The human Herpesvirus type-6 (HHV-6) has been implicated in multiple sclerosis (MS). Valacyclovir is an antiviral agent with an excellent safety profile. A two-year placebo-controlled, double-blind study was conducted to (1) ascertain if high-dose, prolonged treatment with valacyclovir would be safe and (2) observe if valacyclovir would delay the progression of MS clinically or by magnetic resonance imaging (MRI).


METHODS
Fifty-eight patients were stratified as to severity and randomly assigned to receive valacyclovir (3000 mg/day) or placebo for a period of two years. Patients were followed clinically over the two-year period by means of the Expanded Disability Status Scale (EDSS), the Ambulation Index (AI) and brain MRI scans. Patients underwent routine lab studies every three months. Patients continued on the medication for two years unless they had a sustained progression or repeated exacerbations.


RESULTS
No patient discontinued the study due to side effects or toxicity. In Relative Ranking of Progression, time to first attack, attack rate, and time to withdrawal there were trends (but not statistically significant) toward drug effect over placebo in the Severe clinical category. MRI evaluation showed no significant drug effect.


CONCLUSIONS
Although not statistically significant, positive trends were detected for acyclovir by clinical measures, but not by MRI.
Friedman
J E
JE
Department of Neurology, New York University School of Medicine, NY, NY 10010, USA. jef4@med.nyu.edu
Zabriskie
J B
JB
Plank
C
C
Ablashi
D
D
Whitman
J
J
Shahan
B
B
Edgell
R
R
Shieh
M
M
Rapalino
O
O
Zimmerman
R
R
Sheng
D
D
D000212:Acyclovir / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004185:Disability Evaluation; D005260:Female; D005684:Gait; D015654:Herpesvirus 6, Human; D006801:Humans; D007075:Immunoglobulin M / Q000097:blood; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020528:Multiple Sclerosis, Chronic Progressive / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D010865:Pilot Projects; D019349:Roseolovirus Infections / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D000077483:Valacyclovir; D014633:Valine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives*
D000998:Antiviral Agents; D007075:Immunoglobulin M; D014633:Valine; D000077483:Valacyclovir; D000212:Acyclovir