Clinical Trial: Possible Role of Chloroquine to Induce a Complete Remission in the Treatment of Autoimmune Hepatitis: a Randomized Trial
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: Possible Role of Chloroquine in Conjunction to Prednisone to Induce a Complete Remission in the Treatment of Autoimmune Hepatitis: a Randomized Trial
Brief Summary: The gold-standard treatment of Autoimmune hepatitis (AIH), with prednisone alone or in conjunction with azathioprine can reach resolution of the disease in 70-80% of the cases in US. However, in Brazil the response to these treatments seems to be worse, approximately 35% in five years. Because of the side effects of the gold-standard treatment and the need for an alternative option for the no responsive patients, news drugs must be evaluated for this proposal. Chloroquine diphosphate is an antimalarial drug that has been used for the treatment of rheumatological diseases for at the least five decades. Chloroquine was used as a single drug for up to two years for the maintenance of AIH remission in an open study. There was a 6.49 greater chance of relapse in the historical controls when compared with patients treated with chloroquine (72.2% x 23.5%; p = 0.031). The aim of this study was to investigate whether chloroquine in conjunction with prednisone can be used as an alternative treatment of AIH in a randomized study, and to evaluate its side effects.
Detailed Summary:
Autoimmune hepatitis (AIH) is a chronic disease with a progressive destruction of hepatic parenchyma, leading to cirrhosis and high mortality in the absence of specific treatment. It has been demonstrated that the treatment with corticosteroids and azathioprine provides clinical and laboratory improvement, reduction of histological inflammatory activity on liver biopsy and an increased survival.
Because of the side effects of the gold-standard treatment and the need for an alternative option for the no responsive patients, news drugs must be evaluated for this proposal.
Chloroquine is a drug of the group of 4-aminoquinolines, synthetic derivatives of quinine and constituent of the bark of the Cinchona tree. Chloroquine accumulates in tissues in considerable amounts. In animals, from 200 to 700 times the plasma concentration can be found in liver, spleen, kidneys and lungs. As a weak base, it accumulates intracellularly, particularly in lysosomes with a consequent increase in pH within these organelles, which could contribute to its toxicity. Lysosomal lamellar bodies are observed in tissues affected by chloroquine, such as retina and neuromuscular system. Chloroquine inhibits the absorption and the binding of mitochondrial calcium, alters the membrane permeability and the transport of enzymes to the lysosomes. Apparently there are other mechanisms to explain its anti-inflammatory action; such as the interference with the release of TNF from mononuclear phagocytes by inhibiting gene expression and the down-regulation of TNF receptors, by delaying their transport to the cellular surface. Due to these mechanisms of action, chloroquine has anti-inflammatory activities and therefore is used in diseases such as rheumatoid arthritis and systemic lupus erythematosus. In liver diseases, chloroquine was used in patients with hepatit
Sponsor: University of Sao Paulo General Hospital
Current Primary Outcome: Biochemical Response to Therapy [ Time Frame: six months ]
Original Primary Outcome: Biochemical Response to Therapy [ Time Frame: six months ]
Current Secondary Outcome: Histopathological Response to Therapy [ Time Frame: liver biopsy was was performed to evaluate histopathological response after 18 months of biochemical response ]
Original Secondary Outcome: Histopathological Response to Therapy [ Time Frame: eighteen months after bichemical response ]
Information By: University of Sao Paulo General Hospital
Dates:
Date Received: May 18, 2015
Date Started: May 2003
Date Completion:
Last Updated: December 29, 2016
Last Verified: December 2016
