Armodafinil for Patients Starting Hepatitis C Virus Treatment

Armodafinil for Patients Starting Hepatitis C Treatment

Fatigue is one of the most common side effects of the treatment of hepatitis C infection with pegylated interferon and ribavirin, and is a major cause of treatment discontinuation. Armodafinil is an FDA approved stimulant medication for the treatment of narcolepsy and shift-work sleep disorder. This is a randomized placebo controlled study to determine whether patients assigned to armodafinil have fewer missed doses, dose reductions or treatment discontinuation due to side effects in the first 12 weeks of treatment for hepatitis C infection than do placebo patients. Placebo patients are offered 14 weeks of open label armodafinil after Week 12.

Study Overview

• Status: Terminated
• Conditions: Hepatitis C
• Intervention / Treatment: Drug: Armodafinil; Drug: Sugar Pill

Detailed Description

Four million Americans have chronic hepatitis C (HCV), and 30% of HIV+ patients are co-infected with HCV. Until May 2011, the standard treatment for HCV was the combination of alpha interferon (injected weekly) and ribavirin (daily pills) (IFN/RBV) for 48 weeks in order to achieve sustained virologic remission (cure). HCV treatment initiation was low, often because of concern about severe treatment side effects as well as high rates of virologic failure. Among the minority of medically eligible HCV+ patients (with or without co-morbid HIV/AIDS) who actually began treatment with IFN/RBV, side effects cause substantial attrition (about 20% by Week 12, 40% by Week 24). The most common adverse events are flu-like symptoms, of which fatigue is most prominent. Depressed mood is also common (mostly somatic symptoms).

Two new medications, telaprevir and boceprevir (protease inhibitors) have been successful in treatment of HCV in clinical trials, and both were approved by the FDA for those patients with genotype 1 HCV, and are marketed as of May 2011. One of the new drugs will be added to the current regimen for genotype 1 infection. Because both drugs are protease inhibitors, which develop rapid resistance when administered alone, they must be added to the current standard of care rather than replace it. This is expected to vastly increase willingness of doctors to recommend treatment, and for patients to agree to treatment. The investigators expect that most hepatologists will recommend, and patients agree to the addition of one of these medications from now on. However, it should be noted that both commonly cause fatigue if it isn't already present because of HCV itself, or peginterferon or ribavirin. The major adverse event associated with telaprevir is rash, and with boceprevir, anemia.

This is a 14-week placebo controlled double blind trial of armodafinil for patients about to begin HCV treatment, starting armodafinil or placebo 2 weeks prior to initiation of HCV treatment. Patients are recruited from the hepatology clinics at the respective sites. Randomization is 1:1. Placebo patients who continue HCV treatment are offered 14 weeks of armodafinil starting at Week 12 of HCV treatment when the armodafinil/placebo blind is broken.

Patients will be seen weekly for the first 4 weeks to titrate armodafinil dose and manage side effects, if any, and then biweekly, with telephone contact on the intervening weeks through Week 12. After that, monthly telephone calls through Week 24 will be conducted with patients randomized to armodafinil, and biweekly visits with placebo patients beginning armodafinil at Week 12.

The primary outcome measures concern non-adherence to INF/RBV treatment: 1) missed doses; 2) dose reductions, and 3) attrition due to side effects. Secondary outcomes include ratings of fatigue on the Fatigue Severity Scale, depression on the Patient Health Questionnaire (PHQ-9), and quality of life on the Endicott Quality of Life Enjoyment and Satisfaction Questionnaire.

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York City, New York, United States, 10029
      • Mount Sinai Medical Center
    • New York City, New York, United States, 10065
      • New York-Presbyterian/Weill Cornell Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• HCV+ patients medically cleared for IFN/RBV treatment -HIV+ or HIV-
• Speaks English
• Able and willing to give informed consent
• Fecund women: use barrier method of contraception

Exclusion Criteria:

• Untreated and uncontrolled hypertension
• Left ventricular hypertrophy
• Currently taking stimulant medication
• Uncontrolled mental health problems including: MDD, suicidal or homicidal ideation, bipolar disorder, or schizophrenia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Armodafinil; Active medication	Drug: Armodafinil; 50mg - 250mg pills, taken each morning, for 14 weeks; Other Names: Nuvigil
Placebo Comparator: Sugar pill; Inactive pill, matched to look like active medication	Drug: Sugar Pill; Inactive pill, matched to look like active medication; Other Names: Placebo Comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adherence to Medications Form	The Medication Adherence Form was designed to assess any HCV medication dosing changes, including discontinuation, and the reasons for the changes. The form asks specifically about the HCV medications: pegylated interferon, ribavirin and Incivek (or Victrelis), as well as the study medication, armodafinil.	HCV medication adherence reported at 12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fatigue Severity Scale (FSS)	Fatigue Severity Scale is a 9-item scale measures the impact of fatigue on everyday functioning (e.g. "fatigue interferes with my work, family or social life"). Response format is a 7-point Likert scale of agreement with a 1-week time frame. Total score is the sum of item scores and ranges from 9 to 63 points, with higher scores indicating greater fatigue. A score greater than 40 is considered to be a clinically significant level of fatigue. Scores on the scale correlate highly with other measures of fatigue, is sensitive to change, and is routinely used in studies of modafinil/armodafinil.	Biweekly for the first month, monthly thereafter

Collaborators and Investigators

• Sponsor: Research Foundation for Mental Hygiene, Inc.
• Collaborators: Icahn School of Medicine at Mount Sinai; Weill Medical College of Cornell University
• Investigators: Principal Investigator: Jeffrey Weiss, Ph.D., MS, Icahn School of Medicine at Mount Sinai; Principal Investigator: Stephen J. Ferrando, M.D., Weill Medical College of Cornell University

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): June 1, 2014

Study Registration Dates

• First Submitted: October 13, 2011
• First Submitted That Met QC Criteria: November 10, 2011
• First Posted (Estimate): November 11, 2011

Study Record Updates

• Last Update Posted (Actual): February 10, 2017
• Last Update Submitted That Met QC Criteria: December 19, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Fatigue; HCV+; HCV treatment; patients starting alpha interferon/ribavirin treatment
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Hepatitis; Hepatitis A; Hepatitis C; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Central Nervous System Stimulants; Wakefulness-Promoting Agents; Modafinil
• Other Study ID Numbers: C10953/6285

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO