Influenza Challenge in Mood Disorders

NCT02415166 | Terminated Results

• 1 other identifier: LIBR # 2015-001-00
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of this project is to evaluate the efficacy of the influenza vaccine in individuals with major depressive disorder (MDD) as well as to elucidate the nature of the immunological abnormalities in MDD using a quasi-experimental design. Specifically, the investigators plan to induce transient, mild inflammation in medically-healthy study participants using the influenza vaccine. Initially the investigators will conduct a pilot project with up to 20 individuals in order to evaluate the time-point at which the peak inflammatory response to the vaccine occurs. Subjects will receive the seasonal influenza vaccine and provide blood samples 4 hours, 2 days, and 30 days post vaccination. Subsequent to the pilot study, both depressed and psychiatrically-healthy participants will be randomized in a parallel group, double-blind design so that they receive either influenza vaccine (seasonal vaccine) or saline (i.m). At baseline, subjects will provide a blood sample, complete a number of rating scales to measure mood and fatigue, and may complete approximately one hour of MRI scanning with or without simultaneous EEG recording. Two-days post vaccination, they will provide a second blood sample, complete more clinical ratings and may complete another identical MRI session with or without simultaneous EEG. Four weeks later, participants will be asked to return to provide a third blood sample and complete additional clinical ratings. The blood samples will be used to measure both innate and adaptive immune function and may be used to correlate the vaccine-induced immunological changes to neurophysiological changes in the brain measured by MRI and/or EEG.

Conditions

MAJOR DEPRESSIVE DISORDER

Outcome Measures

Primary Outcomes (1)

• THE TITER OF INFLUENZA ANTIBODIES

  Outcome data were not collected. This was a failed study as all participants, including those who were putatively vaccine-naive had antibodies to influenza at baseline and therefore the original hypothesis could not be tested. The study was terminated.

  ONE MONTH

Secondary Outcomes (1)

• THE INFLUENZA VIRUS-INDUCED PROLIFERATION OF CD4+ MEMORY T-CELLS

  ONE MONTH

Other Outcomes (3)

• IL-6 AND TNF PRODUCTION BY STIMULATED AND UNSTIMULATED MONOCYTE CELLS

  2 DAYS

• DIFFERENCES IN RESTING STATE CEREBRAL BLOOD FLOW BETWEEN MDD AND HC GROUPS

  2 DAYS

• DIAGNOSTIC GROUP DIFFERENCES IN THE BOLD RESPONSE (Using fMRI) TO MONETARY REWARDS IN THE VENTRAL STRIATUM

  2 DAYS

Study Arms (4)

VACCINE MDD

EXPERIMENTAL

SEASONAL INFLUENZA VACCINE (0.5ML) DELIVERED I.M.

Biological: INFLUENZA VACCINE

PLACEBO MDD

PLACEBO COMPARATOR

SALINE (0.5ML) DELIVERED I.M.

Other: NaCl-saline placebo

VACCINE HC

EXPERIMENTAL

SEASONAL INFLUENZA VACCINE (0.5ML) DELIVERED I.M.

Biological: INFLUENZA VACCINE

PLACEBO HC

PLACEBO COMPARATOR

SALINE (0.5ML) DELIVERED I.M.

Other: NaCl-saline placebo

Interventions

INFLUENZA VACCINE BIOLOGICAL

THE PURPOSE OF THE STUDY IS TO EVALUATE THE EFFICACY OF THE SEASONAL INFLUENZA VACCINE IN PEOPLE WITH MAJOR DEPRESSIVE DISORDER

VACCINE HC; VACCINE MDD

NaCl-saline placebo OTHER

placebo

PLACEBO HC; PLACEBO MDD

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Major Depressive Disorder Patient Group - Currently Depressed: Subjects will have met Diagnostic and Statistical Manual of the American Psychiatric Association (DSM-V) criteria for primary MDD in a current major depressive episode and current Hamilton Depression Rating Scale (HAM-D) or Montgomery Asberg Depression Rating Scale (MADRS) score in the mild-to-severely depressed range and will have been deemed to be medically stable by a physician listed on this protocol. Subjects who do not wish to receive treatment with psychotropic medication in the future and have not taken psychotropic medication for at least 3 weeks will be included in the study.
• Healthy Comparison Group: Subjects will be selected who have not met criteria for any Axis I psychiatric disorder, have no known first-degree relatives with mood or anxiety disorders, and have a current score on the HAM-D or MADRS in the non-depressed range.

You may not qualify if:

• Inability to provide informed consent, pregnant or nursing women, known hypersensitivity to vaccines, age of onset of MDD \> 40 years, metal implants or other factors that would preclude MRI scanning, serious risk of suicide, delusions or hallucinations, medical or neurological illnesses (such as diabetes, autoimmune disorders or inflammatory bowel disease) that affect brain structure, function or immune measurements, previous head injury with loss of consciousness, abuse of drugs or alcohol within the previous year or a lifetime history of substance dependence, treatment with medications that impact immune function (e.g. prednisone), HIV or other chronic infection, a recent acute illness (e.g. influenza), receipt of a vaccine within 3 months of commencing the study. Subjects whose first major depressive episodes arose temporally after other major medical or psychiatric conditions will also be excluded, since their functional imaging results generally differ from those reported in primary MDD.

Sponsors & Collaborators

• Laureate Institute for Brain Research, Inc.: lead

Study Sites (1)

Laureate Institute for Brian Research

Tulsa, Oklahoma, 74136, United States

Location

Related Publications (8)

• Irwin MR, Miller AH. Depressive disorders and immunity: 20 years of progress and discovery. Brain Behav Immun. 2007 May;21(4):374-83. doi: 10.1016/j.bbi.2007.01.010. Epub 2007 Mar 13.

  PMID: 17360153 BACKGROUND

• Blume J, Douglas SD, Evans DL. Immune suppression and immune activation in depression. Brain Behav Immun. 2011 Feb;25(2):221-9. doi: 10.1016/j.bbi.2010.10.008. Epub 2010 Oct 16.

  PMID: 20955778 BACKGROUND

• Dantzer R, O'Connor JC, Freund GG, Johnson RW, Kelley KW. From inflammation to sickness and depression: when the immune system subjugates the brain. Nat Rev Neurosci. 2008 Jan;9(1):46-56. doi: 10.1038/nrn2297.

  PMID: 18073775 BACKGROUND

• Price JL, Drevets WC. Neurocircuitry of mood disorders. Neuropsychopharmacology. 2010 Jan;35(1):192-216. doi: 10.1038/npp.2009.104.

  PMID: 19693001 BACKGROUND

• Robinson OJ, Cools R, Carlisi CO, Sahakian BJ, Drevets WC. Ventral striatum response during reward and punishment reversal learning in unmedicated major depressive disorder. Am J Psychiatry. 2012 Feb;169(2):152-9. doi: 10.1176/appi.ajp.2011.11010137.

  PMID: 22420038 BACKGROUND

• Savitz J, Drevets WC. Bipolar and major depressive disorder: neuroimaging the developmental-degenerative divide. Neurosci Biobehav Rev. 2009 May;33(5):699-771. doi: 10.1016/j.neubiorev.2009.01.004. Epub 2009 Jan 21.

  PMID: 19428491 BACKGROUND

• Eisenberger NI, Berkman ET, Inagaki TK, Rameson LT, Mashal NM, Irwin MR. Inflammation-induced anhedonia: endotoxin reduces ventral striatum responses to reward. Biol Psychiatry. 2010 Oct 15;68(8):748-54. doi: 10.1016/j.biopsych.2010.06.010. Epub 2010 Aug 16.

  PMID: 20719303 BACKGROUND

• Harrison NA, Brydon L, Walker C, Gray MA, Steptoe A, Critchley HD. Inflammation causes mood changes through alterations in subgenual cingulate activity and mesolimbic connectivity. Biol Psychiatry. 2009 Sep 1;66(5):407-14. doi: 10.1016/j.biopsych.2009.03.015. Epub 2009 May 7.

  PMID: 19423079 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Influenza Vaccines

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Limitations and Caveats

This was a failed study as all participants, including those who were putatively vaccine-naive had antibodies to influenza at baseline and therefore the original hypothesis could not be tests. The study was terminated.

Results Point of Contact

• Title: Jonathan Savitz
• Organization: LaurateInstitute

jsavitz@laureateinstitute.org

918 502 5104

Study Officials

• Jonathan B Savitz, PhD

  Laureate Institute for Brain Research

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 8, 2015
• First Posted: April 14, 2015
• Study Start: July 1, 2015
• Primary Completion: March 1, 2016
• Study Completion: March 1, 2016
• Last Updated: January 23, 2018
• Results First Posted: December 26, 2017

Record last verified: 2017-12

Locations

US (1)