CHLOROQUINE FOR MAINTENANCE REMISSION OF AUTOIMMUNE HEPATITIS

Study Description

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Brief Summary:

Autoimmune hepatitis is an autoimmune chronic liver disease whose treatment includes the use of immunosuppressive drugs, particularly azathioprine, and corticosteroids. When properly treated, patients have a good survival. One of the major problems related to its treatment is the the high rate of relapses after stopping therapy that has lead to biochemical and histological remissions, close to 80%. Many authors recommend continuous treatment throughout life, resulting in the occurrence of many side effects. Chloroquine is a drug with anti-inflammatory properties already used in the treatment of other extrahepatic autoimmune liver diseases. There are some reports in the literature about its beneficial use in liver diseases such as chronic hepatitis B, and a pilot study in patients with autoimmune hepatitis, in which its use was associated with a 6.49 times lower risk of disease recurrence when compared with patients in whom treatment was discontinued after remission. Our purpose is to investigate, in a double-blind randomized trial with placebo, whether chloroquine prevents the recurrence of AIH in patients with histological remission after discontinuation of conventional treatment and to evaluate the occurrence of side effects.

Condition or disease	Intervention/treatment	Phase
Hepatitis, Autoimmune	Drug: Chloroquine diphosphate 250mg; Drug: Placebo	Phase 4

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Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	61 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Double (Participant, Investigator)
Primary Purpose:	Treatment
Official Title:	DOUBLE-BLIND RANDOMIZED CLINICAL TRIAL WITH CHLOROQUINE VERSUS PLACEBO FOR MAINTENANCE OF REMISSION OF AUTOIMMUNE HEPATITIS
Study Start Date :	February 2002
Actual Primary Completion Date :	November 2013
Actual Study Completion Date :	June 2015

Arms and Interventions

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Arm	Intervention/treatment
Active Comparator: Chloroquine diphosphate; chloroquine diphosphate 250mg/day	Drug: Chloroquine diphosphate 250mg; Sugar pill (placebo) one pill per day for 1110 days Chloroquine diphosphate 250mg per day for 1110 days
Placebo Comparator: sugar pill; sugar pill	Drug: Placebo

Outcome Measures

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Primary Outcome Measures :

1. Recurrence of autoimune hepatitis after treatment withdrawal in patients maintained only with chloroquine [ Time Frame: thirty-six months after immunosuppressive treatment withdrawal and initial use of chloroquine ]
   To evaluate the rate of recurrence of autoimmune hepatitis with histological remission after withdrawal of corticosteroids and immunosuppressive drugs and after introduction of maintenance therapy with chloroquine or placebo. Recurrence is defined by the sustained increase or progressive liver enzymes above twice the upper normal reference value (as defined by the criteria of the International Autoimmune Hepatitis) in at least two different dosages taken with an interval of 15 to 30 days.

Secondary Outcome Measures :

1. Side effects of chloroquine [ Time Frame: thirty-six months after immunosuppressive treatment withdrawal and initial use of chloroquine ]
   To assess the occurrence of side effects of chloroquine and to evaluate if the use of chloroquine has a cost benefit for maintenance of remission histological, we will investigate hematological, dermatological, opthalmological, neurological, musculoeskeletal and gastrintestinal symptoms. To evaluate the ocular toxicity, patients will undergo ophthalmic evaluation to detect retinal deposits of chloroquine every six months. Other side effects will be assessed in each medical consultation from the speech of patients and clinical examination.If necessary exams will be performed to confirm the diagnosis (eg electromyography in cases of suspected peripheral neuropathy by chloroquine)
2. Side effects of chloroquine [ Time Frame: thirty-six months after immunosuppressive treatment withdrawal and initial use of chloroquine ]

   To assess the occurrence of side effects of chloroquine and to evaluate if the use of chloroquine has a cost benefit for maintenance of remission histological. We will investigate hematological, dermatological, opthalmological, neurological, musculoeskeletal and gastrintestinal symptoms.

   To evaluate ocular toxicity, patients will undergo ophthalmic evaluation to detect retinal deposits of chloroquine every six months. Other side effects will be assessed in each medical consultation from the talking of patients and clinical examinations. If necessary, other complementary exams will be performed to confirm the diagnosis (for instance, electromyography in cases of suspected peripheral neuropathy by chloroquine).

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 70 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria: - diagnosis of autoimmune hepatitis according to Autoimmune Hepatitis International Group

• histological remission during treatment with immunosuppressive drugs (Liver biopsy with periportal inflammatory activity less than 2)
• No evidence of decompensated liver cirrhosis
• Non-pregnant women and women with no intention to become pregnant
• Willing to participate in the study

Exclusion Criteria:

• patients who needed to suspend the drug under six months of the medication because of side effects or the patient's desire
• cases of loss of follow up

Contacts and Locations

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Locations

Brazil
University of São Paulo School of Medicine
Sao Paulo, Brazil, 05403-010

Sponsors and Collaborators

University of Sao Paulo General Hospital

Investigators

Principal Investigator:	Débora R Terrabuio, master	University of Sao Paulo

More Information

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Publications:

Mucenic M, Mello ES, Cançado EL. Chloroquine for the maintenance of remission of autoimmune hepatitis: results of a pilot study. Arq Gastroenterol. 2005 Oct-Dec;42(4):249-55. Epub 2006 Jan 19.

Responsible Party:	DÉBORA RAQUEL BENEDITA TERRABUIO, MD, University of Sao Paulo General Hospital
ClinicalTrials.gov Identifier:	NCT01980745 History of Changes
Other Study ID Numbers:	CAPPesq 0697/07; 0697/07 ( Other Identifier: Ethics Committee for Analysis of Research Projects HCFMUSP )
First Posted:	November 11, 2013
Last Update Posted:	October 26, 2016
Last Verified:	October 2016

Keywords provided by DÉBORA RAQUEL BENEDITA TERRABUIO, University of Sao Paulo General Hospital:

autoimmune hepatitis; recurrence; treatment withdrawal; chloroquine; maintenance of remission

Additional relevant MeSH terms:

Hepatitis; Hepatitis A; Hepatitis, Autoimmune; Liver Diseases; Digestive System Diseases; Hepatitis, Viral, Human; Virus Diseases; Enterovirus Infections; Picornaviridae Infections; RNA Virus Infections; Hepatitis, Chronic; Autoimmune Diseases; Immune System Diseases; Chloroquine; Chloroquine diphosphate	Amebicides; Antiprotozoal Agents; Antiparasitic Agents; Anti-Infective Agents; Antimalarials; Antirheumatic Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Analgesics; Sensory System Agents; Peripheral Nervous System Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Filaricides; Antinematodal Agents