Relative-dose-response Test (RDR) Adaptation for Chronic Liver Disease

Responsiveness of RDR Test to Assess Hepatic Vitamin A Stores in Chronic Liver Disease

The relative-dose-response test (RDR) is considered to be the most accurate method for evaluating vitamin A nutritional status (VANS) in patients suffering from liver disease, as it infers the reserves of the vitamin in the liver. However, for the RDR test to reflect VANS in patients suffering from chronic liver disease, factors inherent to the disease need to be considered, such as possible malabsorption, advanced age, a drop in synthesis and/or the release of retinol binding protein (RBP), which would result in an inadequate response to the RDR test. Thus, the objective of present study is to assess the adequacy of two different protocol for using the RDR test in patients with cirrhosis and cirrhosis-related hepatocellular carcinoma.

Methods: The sample group was comprised of 178 patients at Federal University of Rio de Janeiro University Hospital (111 men) with several etiologies of liver cirrhosis at different stages in the progression of the disease. They were sorted into two groups, according to the retinyl palmitate dosage (1500 IU or 2500 IU) received at T0 (blood sample taken following a 12-hour fast). Following supplementation, the investigators took further blood samples five and seven hours later (T5 and T7). The investigators assessed VANS via concentrations of serum retinol and RBP, as well as by way of the RDR test. The cutoff points the investigators used for denoting inadequacy in the indicators retinol and RDR were, respectively, < 1.05 µmol/L and ≥ 20%. To classify the degrees of severity of the disease the investigators used the criteria established by Child & Pugh (1973).

Study Overview

• Status: Completed
• Conditions: Chronic Liver Disease
• Intervention / Treatment: Dietary supplement: retinyl palmitate (UNICEF, Melbourne, Australia)

• Study Type: Interventional
• Enrollment (Actual): 178
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Brazil
  • RJ
    • Rio de Janeiro, RJ, Brazil, 22010050
      • Gabriela Villaça Chaves

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diagnosis of liver cirrhosis of viral etiology, alcoholic or metabolic action

Exclusion Criteria:

• malabsorption syndromes
• moderate or severe infection
• diabetes mellitus using insulin renal, cardiac or respiratory
• therapeutic doses of vitamin A in the 6 months prior to data collection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RDR test (1500 UI vitamin A); 81 patients with several etiologies of liver cirrhosis at different stages in the progression of the disease received 1500 UI retinyl palmitate dosage at T0 (blood sample taken following a 12-hour fast). Following supplementation, we took further blood samples five and seven hours later (T5 and T7).	Dietary supplement: retinyl palmitate (UNICEF, Melbourne, Australia); the patients received an oral dose of 1500 IU or 2500 IU, once.; Other Names: vitamin A
Experimental: RDR test (2500 IU vitamin A); 81 patients with several etiologies of liver cirrhosis at different stages in the progression of the disease received 2500 UI retinyl palmitate dosage at T0 (blood sample taken following a 12-hour fast). Following supplementation, we took further blood samples five and seven hours later (T5 and T7).	Dietary supplement: retinyl palmitate (UNICEF, Melbourne, Australia); the patients received an oral dose of 1500 IU or 2500 IU, once.; Other Names: vitamin A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from Baseline in retinol status (RDR test) at 5 and/or 7 hour after supplementation	Therapeutic response is evaluated by means of circulating serum retinol, 5 and 7 hours after the administration of vitamin A. The RDR was calculated by the following formula, using the values of serum retinol in the three times of blood collection (Loerch et al., 1979), expressed in percentages: RDR (%) = [(A0-Ax) / Ax] x100 where A0 is the serum retinol at time 0 (fasting) and Ax is the serum retinol 5 or 7 h after administration of vitamin A. It was used as the RDR cutoff ≥ 20%, indicating indirect hepatic reserve inadequate	RDR will be calculated for the two intervention groups (1500 or 2500 IU vitamin A), for the two moments of blood sampling, 5 and 7 hours after supplementation.

Secondary Outcome Measures

Outcome Measure	Time Frame
serum retinol-binding protein (RBP)	RBP were analyzed at baseline, 5 and 7 hours after supplementation as a variable that explain the appropriate response or failure to respond to the RDR test.

Collaborators and Investigators

• Sponsor: Universidade Federal do Rio de Janeiro
• Investigators: Principal Investigator: Gabriela V Chaves, PhD, Universidade Federal do Rio de Janeiro

Publications and helpful links

General Publications

• Peres WA, Chaves GV, Goncalves JC, Ramalho A, Coelho HS. Vitamin A deficiency in patients with hepatitis C virus-related chronic liver disease. Br J Nutr. 2011 Dec;106(11):1724-31. doi: 10.1017/S0007114511002145. Epub 2011 Jun 8.

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): December 1, 2007
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: June 25, 2012
• First Submitted That Met QC Criteria: July 2, 2012
• First Posted (Estimate): July 6, 2012

Study Record Updates

• Last Update Posted (Estimate): July 6, 2012
• Last Update Submitted That Met QC Criteria: July 2, 2012
• Last Verified: May 1, 2012

More Information

Terms related to this study

• Keywords: cirrhosis; vitamin A; chronic liver disease; RDR test; retinol-binding protein
• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Protective Agents; Micronutrients; Vitamins; Antioxidants; Anticarcinogenic Agents; Vitamin A; Retinol palmitate
• Other Study ID Numbers: CEPHUCFF 06801