Clinical trial NCT01470651: Armodafinil for Patients Starting Hepatitis C Virus Treatment
Official title: Armodafinil for Patients Starting Hepatitis C Treatment
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Hepatitis C
Keywords: HCV+
HCV treatment
Fatigue
patients starting alpha interferon/ribavirin treatment
Lead sponsor: Research Foundation for Mental Hygiene, Inc.
Sponsor class: OTHER
Collaborators: name: Icahn School of Medicine at Mount Sinai
name: Weill Medical College of Cornell University
First posted: 2011-11-11
Enrollment: 26
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Adherence to Medications Form
timeFrame: HCV medication adherence reported at 12 weeks
Secondary outcomes:
measure: Fatigue Severity Scale (FSS)
timeFrame: Biweekly for the first month, monthly thereafter
Other outcomes:
Locations:
city: New York City
country: United States
facility: Mount Sinai Medical Center
state: New York
city: New York City
country: United States
facility: New York-Presbyterian/Weill Cornell Medical Center
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Jeffrey Weiss, Ph.D., MS
role: PRINCIPAL_INVESTIGATOR
affiliation: Weill Medical College of Cornell University
name: Stephen J. Ferrando, M.D.
role: PRINCIPAL_INVESTIGATOR
References: