ANTIVIRAL TREATMENT OF CYTOMEGALOVIRUS IN DEPRESSION

NCT04724447 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: 2021-001
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This study aims to determine whether treatment of CMV positive (CMV+) individuals with major depressive disorder (MDD) with valganciclovir (VGCV) alters neural circuitry, reduces inflammation, and improves depressive behavior and symptoms to a greater extent than placebo. In this double-blind, randomized placebo-controlled, parallel group trial, 24 individuals with a Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR) scale score ≥ 14 will be enrolled to participate in an 8-week treatment study. Participants will be randomized with a 1-1 ratio to receive 900 milligrams (mg) VGCV or placebo to be taken orally once per day. Participants will complete a 2-hour pre-screen, a baseline blood-draw, clinical evaluation, and MRI scan (visit 2), a clinical evaluation, blood draw, and MRI scan at week 4 (visit 6), and a clinical evaluation, blood draw, and MRI scan at week 8 (visit 10). Weekly telephonic visits to assess depressive symptoms and side effects will held between the in-person assessments.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• White matter integrity of the inferior fronto-occipital fasciculus (IFOF)

  Mean fractional anisotropy of the IFOF measured with diffusion tensor imaging

  8 weeks

Secondary Outcomes (1)

• Volume of the medial temporal gyrus (MTG)

  8 weeks

Other Outcomes (5)

• Volume of the orbitofrontal cortex (OFC)

  8 weeks

• Inflammatory mediators

  8 weeks

• CD8+ cells

  8 weeks

Study Arms (2)

Valganciclovir

EXPERIMENTAL

900 milligrams (mg) valganciclovir (VGCV) to be taken orally once per day for 8 weeks.

Drug: Valganciclovir

Placebo

PLACEBO COMPARATOR

Placebo equivalent of 900 milligrams (mg) VGCV to be taken orally once per day for 8 weeks.

Drug: Placebo

Interventions

Valganciclovir DRUG

2 x 450mg VGCV tablets

Valganciclovir

Placebo DRUG

Placebo equivalent of 900mg/day VGCV

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Male or female, aged 18-65 years
• Diagnosis with major depressive disorder (MDD)
• Current symptoms of depression, that is, a QIDS-SR score ≥14.
• Unmedicated for at least 4 weeks (8 weeks for fluoxetine).
• In good general health as evidenced by medical history, physical exam, and safety labs
• Ability to take oral medication and be willing to adhere to the VGCV regimen
• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation and for an additional 4 weeks after the end of VGCV administration
• For males of reproductive potential: use of condoms or other methods to ensure effective contraception with partner during the study and for at least 90 days after the study.
• Agreement to adhere to Lifestyle Considerations (see section 5.3) throughout study duration

You may not qualify if:

• Pregnancy
• Breast-feeding
• Unwillingness to avoid pregnancy during the study due to the possible teratogenic effects of valganciclovir
• Medical Conditions:
• Moderate to severe traumatic brain injury (\>30 min. loss of consciousness or \>24 hours posttraumatic amnesia) or other neurocognitive disorder with evidence of neurological deficits.
• Presence of co-morbid medical conditions not limited to but including cardiovascular (e.g., history of acute coronary event, stroke) and neurological diseases (e.g., Parkinson's disease), as well as pain disorders.
• Presence of co-morbid inflammatory disorders such as rheumatoid arthritis or other autoimmune disorders.
• Presence of an uncontrolled medical condition that is deemed by the investigators to interfere with the proposed study procedures, or to put the study participant at undue risk.
• Presence of a chronic infection (e.g. HIV) that may elevate pro-inflammatory cytokines.
• Presence of an acute infectious illness (e.g. SARS CoV-2) or receipt of a vaccination in the week prior to enrollment.
• Psychiatric Disorders:
• Current significant suicidal ideation (intent to commit suicide or making specific plans for suicide)
• Suicide attempt within the last 6 months
• Lifetime history of schizophrenia, schizophreniform, schizoaffective disorder, delusional disorder
• History of a manic or hypomanic episode not better accounted for by substance use

Sponsors & Collaborators

• Laureate Institute for Brain Research, Inc.: lead

Study Sites (1)

Laureate Institute for Brain Research

Tulsa, Oklahoma, 74136, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Valganciclovir

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Ganciclovir; Acyclovir; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2021
• First Posted: January 26, 2021
• Study Start: November 23, 2021
• Primary Completion: April 1, 2026
• Study Completion: April 1, 2026
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)