Inflammation, Stress & Social Behavior: Using Ecological Assessments & Model Systems to Enhance Relevance to Health Outcomes

Hepatitis C Clinical Trial

Official title:

Inflammation, Stress and Social Behavior: Using Ecological Assessments and Model Systems to Enhance Relevance to Health Outcomes

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT01625793
• Other study ID #: 12-0166-02
• Secondary ID: 5R01AT007297-03
• Status: Withdrawn
• Phase: N/A
• First received: June 11, 2012
• Last updated: July 18, 2013
• Start date: June 2012
• Est. completion date: July 2013

Study information

• Verified date: July 2013
• Source: University of Arizona
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The current study has been designed to identify behavioral and physiological mechanisms through which positive social connectivity (PCS) and negative social processes (NSP) interact with psychosocial stress to promote resilience in the context of illness. The investigators model inflammation (a central element of all disease states) through the use of treatment with interferon (IFN)-alpha, which provides a standardized regimen of chronic cytokine exposure known to produce profound behavioral disturbances, including depression, fatigue and sickness, in a high percentage of individuals. To objectively assess social processes, the current project will employ the Electronically Activated Recorder (EAR), which periodically and unobtrusively records snippets of ambient sounds in people's momentary environments. To objectively assess behavioral and physiological responses to psychosocial stress the current project will employ the Trier Social Stress Test (TSST), a standardized laboratory stressor known to reliably activate behavioral, neuroendocrine and inflammatory responses. These novel methodologies and model systems will be employed to test the hypotheses that (a) pre-existing affiliative and prosocial behavior will promote resilience in the context of chronic inflammation and that (b) —conversely—chronic inflammation will reduce affiliative and prosocial behavior via effects on stress reactivity, neuroendocrine function and sleep. Finally, it will explore (c) the potential mediating role of stress physiology. To test these hypotheses, 110 subjects with chronic hepatitis C virus infection will be randomized to receive treatment with pegylated IFN-alpha plus ribavirin or to postpone treatment for 6 weeks: 55 subjects at University of Arizona and 55 subjects at Emory University. Prior to randomization and 6 weeks later all subjects will be evaluated with the EAR and sleep actigraphy in their home environments and will undergo TSST and 14 hour diurnal neuroendocrine and immune measurement.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: July 2013
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 21 Years to 65 Years

Eligibility

Inclusion Criteria:

• Age 21-65 years including males, females and minorities

• Ability to speak and read remedial English

• Serum positive for either anti-HCV antibodies or HCV-RNA positive by PCR

• Compensated liver disease with the following minimum hematologic and biochemical criteria: hemoglobin =13 g/dl for males; =12 g/dl for females, white blood cell count > 3,000/mm3, neutrophil count >1,5000/mm3, platelets > 100,000/mm3, prothrombin time = 2 seconds prolonged compared to control, or equivalent INR ratio, albumin stable and within normal limits, serum creatinine within normal limits, thyroid-stimulating hormone within normal limits, direct bilirubin = 0.3 mg/dl or within 20% of upper limit of normal (ULN) for local laboratory, indirect bilirubin = 0.8 mg/dl or within 20% of ULN for local laboratory, fasting blood sugar = 115 mg/dl or within 20% of ULN for non-diabetic patients

• Negative pregnancy test for women of childbearing potential, and confirmation and documentation that adequate contraception or monogamous relationship with a male partner who has had a vasectomy during the treatment period and for 6 months after discontinuation of therapy

• Not breastfeeding

• Documentation and confirmation of adequate contraception in sexually active males

• Free from all psychotropic medications for 14 days prior to baseline visit (8 weeks for fluoxetine)

Exclusion Criteria:

• Evidence of untreated or poorly controlled endocrine, cardiovascular, hematological, renal, or neurological disease

• Evidence of decompensated liver disease (such as a history or presence of ascites, bleeding varices, spontaneous encephalopathy)

• History of narcolepsy, PLMS or sleep apnea (or documented during the adaptation night)

• History of CNS trauma or active seizure disorder requiring medication

• Any cause for liver disease other than chronic hepatitis C, such as co-infection with hepatitis B virus and/or human immunodeficiency virus, hemochromatosis, or Wilson's diseases

• Prior treatment with ribavirin or other antiviral or immunomodulatory drugs, including corticosteroids within 6 months of entry into protocol

• Chronic use of agents known to affect monoamine metabolism/function (and hence potentially affect the TSST), including, but not limited to, alpha- and beta-receptor agonists and antagonists, methylphenidate hydrochloride, dextroamphetamine, midodrine hydrochloride, theophylline, ephedrine, systemic antifungal azoles, sumatriptan succinate

• Psychotropic medications within 14 days prior to baseline visit (8 weeks for fluoxetine)

• Clinical gout

• Hypersensitivity to alpha interferon or ribavirin

• Hemoglobinopathies (e.g. thalassemia)

• A positive pregnancy test

• Organ transplants

• A score of <24 on the Mini Mental Status Exam (MMSE)

• Active, effective treatment of depression with an antidepressant within the past six months

• Actively meet criteria for major depression within the past six months

• Meet criteria for schizophrenia or bipolar disorder (mania) past or present

• Active abuse of alcohol or illicit/prescription drugs within the past year any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with participating in or completing the protocol

Study Design

Allocation: Randomized, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Hepatitis C

Intervention

Drug:
• Interferon-alpha
Hepatitis C patients who are eligible to receive IFN-alpha treatment and enrolled in this study will be treated with pegylated IFN-alfa-2b or pegylated IFN-alfa-2a plus ribavirin at a dose of 800-1,400 mg/d as determined by the treating gastroenterologist. All medication administration is for purely clinical indications as dictated by treating physicians. Any and all diagnostic or treatment issues related to potential treatment with IFN-alpha will be conducted by treating clinicians. Subjects will be randomized to start their clinical (non-research) treatment following completion of baseline assessments or to delay the start of their clinical (non-research) treatment by 7 weeks.

Locations

Country	Name	City	State
United States	Emory University	Atlanta	Georgia
United States	University of Arizona	Tucson	Arizona

Sponsors (3)

Lead Sponsor	Collaborator
University of Arizona	Emory University, National Center for Complementary and Integrative Health (NCCIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percent time laughing		7 weeks	No
Primary	Percent time expressing empathy for others		7 weeks	No
Primary	Percent of time spent in substantive conversations		7 weeks	No
Primary	Percent of time spent alone		7 weeks	No
Secondary	Cortisol concentrations in blood in response to stress test		7 weeks	No
Secondary	Interleukin (IL)-6 concentrations in the blood in response to stress test		7 weeks	No
Secondary	Diurnal plasma concentrations of interleukin-6 and tumor necrosis factor-alpha type II receptors in response to a stress test		7 weeks	No
Secondary	Diurnal plasma concentrations of inflamcortisol in response to a stress test		7 weeks	No
Secondary	Wake time after sleep onset measured by actigraphy		7 weeks	No
Secondary	Sleep latency by measured by actigraphy		7 weeks	No
Secondary	Total sleep time by actigraphy		7 weeks	No
Secondary	Sleep efficiency by actigraphy		7 weeks	No
Secondary	Structured Interview Guide for the Hamilton Depression Scale and Inventory of Depressive Symptomatology (SIGH-IDS)		7 weeks	No