An open-label trial of the PPAR-gamma ligand rosiglitazone for active ulcerative colitis.
OBJECTIVE
Previous research has demonstrated that ligands for the gamma subtype of peroxisome proliferator-activated receptors (PPARs) reduce inflammation in two different murine models of colitis. This study was designed to examine the potential efficacy of rosiglitazone, a ligand for the gamma subtype of PPARs, as a therapy for active ulcerative colitis.


METHODS
Fifteen patients with mild to moderately active ulcerative colitis despite therapy with 5-aminosalicylic acid compounds were enrolled in an open-label study of rosiglitazone (4 mg b.i.d. p.o.) for 12 wk. Thirteen of 15 patients were receiving concomitant therapy with corticosteroids and/or immunomodulator medications. Disease activity was measured with the Disease Activity Index.


RESULTS
After 12 wk of therapy, four patients (27%) had achieved clinical remission, of whom three (20%) also had an endoscopic remission. Four additional patients (27%) had a clinical response without achieving remission. Two patients were hospitalized with worsened disease activity, and one patient was withdrawn for nephrotic syndrome.


CONCLUSIONS
These data suggest that ligands for the gamma subtype of PPARs may represent a novel therapy for ulcerative colitis. A double blind, placebo-controlled, randomized trial is warranted.
Lewis
J D
JD
Division of Gastroenterology, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, Philadelphia 19104-6021, USA.
Lichtenstein
G R
GR
Stein
R B
RB
Deren
J J
JJ
Judge
T A
TA
Fogt
F
F
Furth
E E
EE
Demissie
E J
EJ
Hurd
L B
LB
Su
C G
CG
Keilbaugh
S A
SA
Lazar
M A
MA
Wu
G D
GD
D000328:Adult; D000368:Aged; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D003113:Colonoscopy; D005260:Female; D006801:Humans; D008024:Ligands; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012074:Remission Induction; D000077154:Rosiglitazone; D012720:Severity of Illness Index; D013844:Thiazoles / Q000009:adverse effects / Q000378:metabolism* / Q000627:therapeutic use*; D045162:Thiazolidinediones; D014157:Transcription Factors / Q000378:metabolism*
D008024:Ligands; D018160:Receptors, Cytoplasmic and Nuclear; D013844:Thiazoles; D045162:Thiazolidinediones; D014157:Transcription Factors; D000077154:Rosiglitazone