Genetic and Biochemical Markers of Interferon-Induced Depression.

An observational study of Depression, run by US Department of Veterans Affairs at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Trial summary

The purpose of this study is to identify predictors and associated biochemical markers of interferon-induced depression. It is hypothesized that genetic variation in genes related to the serotonergic system may predict vulnerability to interferon-induced depression. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Depression
Type of treatment: Injection or infusion
How many people: 133 participants
Where: 3 sitesUnited States
Study dates: Apr 2006to Sep 2009
Phase: Observational
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Study population: 120 patients initiating interferon therapy will be recruited from the Portland, Minneapolis, and Long Beach VAMCs. The study is limited to only those participants who are currently mentally healthy at baseline and eligible to receive interferon therapy. Research participants are: 1) male or female, 2) age 18 or older, 3) chronically infected with the hepatitis C virus, 4) candidates for interferon therapy, 4) not on antidepressant treatment , and 5) not currently abusing any substances such as alcohol or intravenous drugs, or having abused in the past 6 months

Who may be able to join

Serum positive for hepatitis C
Age 18 or older
Not pregnant and using adequate contraception
Hepatologist-determined patient is a candidate for interferon therapy
Written/signed informed consent specific for this protocol has been obtained prior to entry

Who cannot join

Diagnosis of active: depression, psychotic symptoms, or bipolar disorder (or history of bipolar disorder) during the previous 3 months
On antidepressant medications for any reason
Currently abusing any substances such as alcohol or intravenous drugs, or having abused in the past 6 months.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

VA Medical Center, Long Beach
Long Beach, California, 90822
VA Medical Center, Minneapolis
Minneapolis, Minnesota, 55417
VA Medical Center, Portland
Portland, Oregon, 97201

Other trials in United States

About this study

Read the detailed description

Objective of project: Interferon-a (IFN)-induced depression is a common complication of its use in treating patients for hepatitis C (HCV), with reports of up to 44% of patients experiencing these depressive side effects. The central hypothesis of the proposed research is that polymorphisms in specific serotonergic genes are associated with a propensity to develop IFN-induced depression. Further, IFN-induced decreases in tryptophan and serotonin levels are putatively related to the emergence of depressive symptoms during IFN therapy. The objective of this proposal is to identify predictors of IFN-induced depression such that depressive side effects can be better managed and treated thus permitting patients to complete a full course of IFN therapy.
Research plan: We plan to test our hypothesis and accomplish the objectives of this application by pursuing the following two specific objectives:
to evaluate the role of genetic loci that may contribute to the vulnerability to IFN using association analyses. Vulnerability is operationalized as the maximal Beck Depression Inventory-II (BDI-II) score, co-varying for pre-treatment BDI-II scores, and
to identify the effects and time course of antiviral therapy on potential biomarkers of IFN-induced depression, including tryptophan, 5-HT, and cortisol levels. Changes in biochemical levels will be compared to depressive symptomology and genetic vulnerability.
Methodology: Patients will be asked to participate in a prospective study in which they will be monitored during the course of IFN therapy for symptoms of depression and for biochemical changes measured in their blood. 120 HCV patients initiating IFN therapy will be recruited (3/month for 40 months) from the Portland VA and the Long Beach VA Medical Centers. Following baseline assessments, subjects will be followed every 2 weeks for a period of 4 months. The development of major depression, depressive symptoms, and related IFN-induced side effects will be monitored using rating scales. For genetic and biochemical measures, blood samples will be collected prior to and during IFN therapy. Patients will be tested for certain genetic polymorphisms. Analyses. Using linear regression, genotype will be the independent variable, and co-varying for baseline BDI-II score, the maximal BDI-II score will be examined as a dependent variable. An ANOVA for repeated measures will be performed to determine the effects of IFN therapy on tryptophan, 5-HT, and cortisol levels. In addition, the relationship between interferon induced MDD and certain polymorphisms will be examined.
Findings, results or conclusions reached to date: In preliminary studies we found that 33% of HCV patients on IFN therapy developed major depressive disorder during the course of treatment. In addition, preliminary pilot results suggest that the 5-HT transporter polymorphism short allele and the "C" allele for the tryptophan hydroxylase polymorphism may increase vulnerability to IFN-induced depression.
Clinical relevance: There are currently no known, reliable predictors of IFN-induced depression. The chronic disease of HCV infection collectively affects approximately 4 million Americans and 200 million people worldwide. IFN is the only clinically approved medication whose long-term use can reduce the risk of a fatal outcome and even be curative in some individuals. However, side effects associated with IFN therapy represent a major obstacle to adequate treatment for patients with HCV, often resulting in the discontinuation IFN therapy.

Conditions: Depression
Keywords: Cortisol, Depression, Hepatitis C, Interferon, Polymorphism, Serotonin, Tryptophan
Medical subject headings: Depression, Hepatitis C

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00252538
Study group	Role	What they receive
Group 1		Research participants are: 1) male or female, 2) age 18 or older, 3) chronically infected with the hepatitis C virus, 4) candidates for interferon therapy, 4) not on antidepressant treatment , and 5) not currently abusing any substances such as alcohol or intravenous drugs, or having abused in the past 6 months

What is being measured

The primary outcome is the main question the study is designed to answer.

Phenotype and Genotype Based on Presence of Interferon Induced MDD.
Structured psychiatric interviews and symptom rating scales for depression were used as primary outcome measures to determine the association between phenotype (interferon-induced depression) and genotype (genes that confer risk of interferon-induced depression). Genes of interest related to development of depression and antiviral treatment response that may confer risk for interferon induced depression were examined. this was a multi-site study and included participants from several hospital settings.
Three polymorphisms of the interleukin (IL)-28b gene were examined - the c/c, c/t and t/t - and the relationship to MDD was examined. P-values above 0.05 are considered statistically insignificant in this study.
In a subsequent analysis of only VA participants proinflammatory cytokines and serotonin levels were examined relative to symptoms of depression.
Measured: The proposed enrollment began after funding notification and enrollment will last for a period of 40 months and until end of study.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Apr 2006Sep 2009

First posted11 Nov 2005 (estimated)
Study startApr 2006
Primary completionSep 2009
Study completionSep 2009

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (2)Papers the sponsor has linked to this study.
Other trials for DepressionStudies of the same condition, open and under way.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Observational
Observational model: Cohort
Time perspective: Prospective
Enrolment: 133 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00252538
Sponsor's protocol ID: MHBA-020-04F
Status last verified: Dec 2014
First submitted: 9 Nov 2005
Last updated: 11 Dec 2014
Results posted: Yes, on ClinicalTrials.gov

Publications

Loftis JM, Patterson AL, Wilhelm CJ, McNett H, Morasco BJ, Huckans M, Morgan T, Saperstein S, Asghar A, Hauser P. Vulnerability to somatic symptoms of depression during interferon-alpha therapy for hepatitis C: a 16-week prospective study. J Psychosom Res. 2013 Jan;74(1):57-63. doi: 10.1016/j.jpsychores.2012.10.012. Epub 2012 Nov 21.
PubMed 23272989
Lotrich FE, Loftis JM, Ferrell RE, Rabinovitz M, Hauser P. IL28B polymorphism is associated with both side effects and clearance of hepatitis C during interferon-alpha therapy. J Interferon Cytokine Res. 2011 Mar;31(3):331-6. doi: 10.1089/jir.2010.0074. Epub 2010 Dec 6.
PubMed 21133812

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 11 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Genetic and Biochemical Markers of Interferon-Induced Depression.
ClinicalTrials.gov ID: NCT00252538
Acronym / sponsor ID: MHBA-020-04F
Conditions: Depression
Keywords: Cortisol, Depression, Hepatitis C, Interferon, Polymorphism, Serotonin, Tryptophan
Study type: Observational
Recruitment status: Completed
Enrolment: 133 participants (actual)
Lead sponsor: US Department of Veterans AffairsUS federal agency
Study start: Apr 2006
Primary completion: Sep 2009 (actual)
Study completion: Sep 2009 (actual)
First posted: 11 Nov 2005 (estimated)
Results: Posted 11 Dec 2014

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Objective of project: Interferon-a (IFN)-induced depression is a common complication of its use in treating patients for hepatitis C (HCV), with reports of up to 44% of patients experiencing these depressive side effects. The central hypothesis of the proposed research is that polymorphisms in specific serotonergic genes are associated with a propensity to develop IFN-induced depression. Further, IFN-induced decreases in tryptophan and serotonin levels are putatively related to the emergence of depressive symptoms during IFN therapy. The objective of this proposal is to identify predictors of IFN-induced depression such that depressive side effects can be better managed and treated thus permitting patients to complete a full course of IFN therapy.
Research plan: We plan to test our hypothesis and accomplish the objectives of this application by pursuing the following two specific objectives:
to evaluate the role of genetic loci that may contribute to the vulnerability to IFN using association analyses. Vulnerability is operationalized as the maximal Beck Depression Inventory-II (BDI-II) score, co-varying for pre-treatment BDI-II scores, and
to identify the effects and time course of antiviral therapy on potential biomarkers of IFN-induced depression, including tryptophan, 5-HT, and cortisol levels. Changes in biochemical levels will be compared to depressive symptomology and genetic vulnerability.
Methodology: Patients will be asked to participate in a prospective study in which they will be monitored during the course of IFN therapy for symptoms of depression and for biochemical changes measured in their blood. 120 HCV patients initiating IFN therapy will be recruited (3/month for 40 months) from the Portland VA and the Long Beach VA Medical Centers. Following baseline assessments, subjects will be followed every 2 weeks for a period of 4 months. The development of major depression, depressive symptoms, and related IFN-induced side effects will be monitored using rating scales. For genetic and biochemical measures, blood samples will be collected prior to and during IFN therapy. Patients will be tested for certain genetic polymorphisms. Analyses. Using linear regression, genotype will be the independent variable, and co-varying for baseline BDI-II score, the maximal BDI-II score will be examined as a dependent variable. An ANOVA for repeated measures will be performed to determine the effects of IFN therapy on tryptophan, 5-HT, and cortisol levels. In addition, the relationship between interferon induced MDD and certain polymorphisms will be examined.
Findings, results or conclusions reached to date: In preliminary studies we found that 33% of HCV patients on IFN therapy developed major depressive disorder during the course of treatment. In addition, preliminary pilot results suggest that the 5-HT transporter polymorphism short allele and the "C" allele for the tryptophan hydroxylase polymorphism may increase vulnerability to IFN-induced depression.
Clinical relevance: There are currently no known, reliable predictors of IFN-induced depression. The chronic disease of HCV infection collectively affects approximately 4 million Americans and 200 million people worldwide. IFN is the only clinically approved medication whose long-term use can reduce the risk of a fatal outcome and even be curative in some individuals. However, side effects associated with IFN therapy represent a major obstacle to adequate treatment for patients with HCV, often resulting in the discontinuation IFN therapy.

Study design

Observational model: Cohort
Time perspective: Prospective
Number of arms: 1

Arm	Type	Receives
Group 1	–	–Research participants are: 1) male or female, 2) age 18 or older, 3) chronically infected with the hepatitis C virus, 4) candidates for interferon therapy, 4) not on antidepressant treatment , and 5) not currently abusing any substances such as alcohol or intravenous drugs, or having abused in the past 6 months

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult
Study population: 120 patients initiating interferon therapy will be recruited from the Portland, Minneapolis, and Long Beach VAMCs. The study is limited to only those participants who are currently mentally healthy at baseline and eligible to receive interferon therapy. Research participants are: 1) male or female, 2) age 18 or older, 3) chronically infected with the hepatitis C virus, 4) candidates for interferon therapy, 4) not on antidepressant treatment , and 5) not currently abusing any substances such as alcohol or intravenous drugs, or having abused in the past 6 months

Key inclusion criteria (5 listed)

Serum positive for hepatitis C
Age 18 or older
Not pregnant and using adequate contraception
Hepatologist-determined patient is a candidate for interferon therapy
Written/signed informed consent specific for this protocol has been obtained prior to entry

Key exclusion criteria (3 listed)

Diagnosis of active: depression, psychotic symptoms, or bipolar disorder (or history of bipolar disorder) during the previous 3 months
On antidepressant medications for any reason
Currently abusing any substances such as alcohol or intravenous drugs, or having abused in the past 6 months.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Primary outcome

Phenotype and Genotype Based on Presence of Interferon Induced MDD.
Time frame: The proposed enrollment began after funding notification and enrollment will last for a period of 40 months and until end of study.
Structured psychiatric interviews and symptom rating scales for depression were used as primary outcome measures to determine the association between phenotype (interferon-induced depression) and genotype (genes that confer risk of interferon-induced depression). Genes of interest related to development of depression and antiviral treatment response that may confer risk for interferon induced depression were examined. this was a multi-site study and included participants from several hospital settings. Three polymorphisms of the interleukin (IL)-28b gene were examined - the c/c, c/t and t/t - and the relationship to MDD was examined. P-values above 0.05 are considered statistically insignificant in this study. In a subsequent analysis of only VA participants proinflammatory cytokines and serotonin levels were examined relative to symptoms of depression.

Results and safety

Results posted to the registry on 11 Dec 2014, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Group 1 MDD	19	19
Group 2 Non MDD	114	114

Primary outcome: Phenotype and Genotype Based on Presence of Interferon Induced MDD.

Time frame: The proposed enrollment began after funding notification and enrollment will last for a period of 40 months and until end of study.. Number. Unit: participants

Measure	Group 1- MDD n = 19	Group 2- no MDD n = 114
Value	19	114

Group 1- MDD vs Group 2- no MDD: p >0.05, ANOVA

Population analysed: This is an observational study that segregates patients with HCV and on interferon alpha treatment into 2 groups based on whether they develop major depressive disorder (MDD) while on interferon alpha therapy for HCV and then examines genes that may confer risk for MDD development. group 1 MDD and group 2 no MDD. total sample from multiple sites.

Adverse events

Time frame: 4/6/2006 - 9/1/2009 ( 3 years and 5 months). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Group 1	1 of 133 (0.8%)	0 of 133 (0%)	Not reported

Limitations and caveats (from the sponsor): Limitations include that there are numerous polymorphism in various genes that may influence certain symptoms of depression. The risk for side effects during interferon-alpha treatment likely influenced by many genetic polymorphisms.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2014.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 23272989Loftis JM, Patterson AL, Wilhelm CJ, McNett H, Morasco BJ, Huckans M, Morgan T, Saperstein S, Asghar A, Hauser P. Vulnerability to somatic symptoms of depression during interferon-alpha therapy for hepatitis C: a 16-week prospective study. J Psychosom Res. 2013 Jan;74(1):57-63. doi: 10.1016/j.jpsychores.2012.10.012. Epub 2012 Nov 21.
Results publication: PubMed 21133812Lotrich FE, Loftis JM, Ferrell RE, Rabinovitz M, Hauser P. IL28B polymorphism is associated with both side effects and clearance of hepatitis C during interferon-alpha therapy. J Interferon Cytokine Res. 2011 Mar;31(3):331-6. doi: 10.1089/jir.2010.0074. Epub 2010 Dec 6.
The official website for the American Liver Foundation, which provides educational information and other resources for people with hepatitis C.Link provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Peter Hauser, MD principal investigator

VA Medical Center, Long Beach

3 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

An observational study of Depression, run by US Department of Veterans Affairs at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 11 Dec 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Dec 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phenotype and Genotype Based on Presence of Interferon Induced MDD. (time frame: The proposed enrollment began after funding notification and enrollment will last for a period of 40 months and until end of study.). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00252538, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Dec 2014.