Major Depressive DisorderPhase 1/2NCT04724447
ANTIVIRAL TREATMENT OF CYTOMEGALOVIRUS IN DEPRESSION
A Phase 1/2 study testing Valganciclovir in people with Major Depressive Disorder, run by Laureate Institute for Brain Research, Inc. at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Valganciclovir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- 23 Nov 2021to 1 Apr 2026
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
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- 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
Who cannot join
- General Exclusion Criteria:
- 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.
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- 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
- Moderate to severe substance use disorder within the last year, excluding cannabis or nicotine use disorder
- Moderate or severe alcohol use disorder
- Positive urine toxicology (except cannabis)
- Contraindications to Valganciclovir:
- Myelosuppressive chemotherapy or radiation therapy
- Absolute neutrophil count < 500/mm3
- Platelet count < 25,000/mm3
- Hemoglobin < 8g/dL
- Impaired renal function (estimated glomerular filtration rate <60mL/minute/1.73m2)
- Sensitivity to VGCV, ganciclovir or other nucleoside analogues
- Medications that could interact with VGCV (see below):
- Prohibited Medications Abacavir Lamivudine, 3TC Amikacin Aminoglycosides Amphotericin B cholesteryl sulfate complex (ABCD) Amphotericin B lipid complex (ABLC) Amphotericin B liposomal (LAmB) Amphotericin B Aprotinin Bacitracin Bictegravir; Emtricitabine; Tenofovir Alafenamide Cisplatin Colchicine; Probenecid Cyclosporine Dapsone Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
- Didanosine, ddI:
- Doravirine; Lamivudine; Tenofovir disoproxil fumarate Doxorubicin Efavirenz; Emtricitabine; Tenofovir Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate Emtricitabine Emtricitabine; Rilpivirine; Tenofovir alafenamide Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate Emtricitabine; Tenofovir alafenamide Emtricitabine; Tenofovir disoproxil fumarate Entecavir Flucytosine Gentamicin Hyaluronidase, Recombinant; Immune Globulin Hydroxyurea Imipenem; Cilastatin Immune Globulin IV, IVIG, IGIV Kanamycin Lamivudine; Tenofovir Disoproxil Fumarate Mycophenolate Paromomycin Pentamidine Plazomicin Polymyxin B Streptomycin Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole Tacrolimus Talimogene Laherparepvec Telbivudine Tenofovir Alafenamide Tenofovir, PMPA Tobramycin Trimethoprim Vancomycin Vinblastine Vinca alkaloids Vincristine Liposomal Vincristine Vinorelbine Zidovudine
- Other Medications:
- Current and/or past regular use of hormone-containing medications (excluding contraceptives)
- Current use of non-steroid anti-inflammatory drugs that is deemed by the investigators to potentially confound the results of the study or the increase risk of renal impairment (e.g. more than 3 days/week).
- Current and/or past regular use of immune modifying drugs that target specific immune responses such as TNF antagonists
- Chronic use of antibiotics such as isotretinoin or minocycline because of their potential effects on the microbiome and immune function.
- Current and/or past regular use of antiarrhythmic, anti-anginal, and anticoagulant drugs (does not apply where medications are taken for different purpose).
- Inclusion of individuals reporting other types of medications or supplements not listed or considered thus far will be at the discretion of the PI based on their potential to affect immune function, brain function or brain blood flow.
- Contraindications to MRI:
- Cardiac pacemaker, metal fragments in eyes/skin/body (shrapnel), aortic/aneurysm clips, prosthesis, by-pass surgery/coronary artery clips, hearing aid, heart valve replacement, shunt (ventricular or spinal), electrodes, metal plates/pins/screws/wires, or neuro/bio-stimulators (TENS unit), persons who have ever been a professional metal worker/welder, history of eye surgery/eyes washed out because of metal, vision problems uncorrectable with lenses, inability to lie still on one's back for 60 minutes; prior neurosurgery; tattoos or cosmetic makeup with metal dyes, unwillingness to remove body piercings, and pregnancy.
- Claustrophobia severe enough to prevent scanning
- Health Factors:
- BMI > 38 because of the effects of obesity on pro-inflammatory cytokine activity
- Clinically significant abnormalities on screening laboratory tests
- Non-English speaking participants:
- The majority of the assessments proposed for this study have not been translated from English, thus, non-English speaking volunteers will be excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
Laureate Institute for Brain Research
Tulsa, Oklahoma, 74136
About this study
Official title: EXPERIMENTAL ANTIVIRAL TREATMENT OF CYTOMEGALOVIRUS IN DEPRESSION: AFFECTIVE, NEURAL, AND INFLAMMATORY MECHANISMS
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
- Being tested
- Valganciclovir, Placebo
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ValganciclovirDrug
2 x 450mg VGCV tablets
PlaceboDrug
Placebo equivalent of 900mg/day VGCV
| Study group | Role | What they receive |
|---|---|---|
| Valganciclovir | Experimental | 900 milligrams (mg) valganciclovir (VGCV) to be taken orally once per day for 8 weeks. Receives: Drug: Valganciclovir |
| Placebo | Placebo comparator | Placebo equivalent of 900 milligrams (mg) VGCV to be taken orally once per day for 8 weeks. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
White matter integrity of the inferior fronto-occipital fasciculus (IFOF)
Mean fractional anisotropy of the IFOF measured with diffusion tensor imaging
Measured: 8 weeks
Secondary outcomes (1)
Volume of the medial temporal gyrus (MTG)
Mean gray matter volume of the MTG measured with structural MRI
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jan 2021
- Study start23 Nov 2021
- Primary completion1 Apr 2026
- Study completion1 Apr 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies 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
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Laureate Institute for Brain Research, Inc.
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04724447
- Sponsor's protocol ID
- 2021-001
- Status last verified
- Apr 2026
- First submitted
- 22 Jan 2021
- Last updated
- 21 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- EXPERIMENTAL ANTIVIRAL TREATMENT OF CYTOMEGALOVIRUS IN DEPRESSION: AFFECTIVE, NEURAL, AND INFLAMMATORY MECHANISMS
- ClinicalTrials.gov ID
- NCT04724447
- Acronym / sponsor ID
- 2021-001
- Conditions
- Major Depressive Disorder
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Laureate Institute for Brain Research, Inc.University, hospital or other
- Study start
- 23 Nov 2021 (actual)
- Primary completion
- 1 Apr 2026 (actual)
- Study completion
- 1 Apr 2026 (actual)
- First posted
- 26 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Valganciclovir | Experimental | Drug: Valganciclovir900 milligrams (mg) valganciclovir (VGCV) to be taken orally once per day for 8 weeks. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo equivalent of 900 milligrams (mg) VGCV to be taken orally once per day for 8 weeks. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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.
Key exclusion criteria (45 listed)
- Prohibited Medications Abacavir Lamivudine, 3TC Amikacin Aminoglycosides Amphotericin B cholesteryl sulfate complex (ABCD) Amphotericin B lipid complex (ABLC) Amphotericin B liposomal (LAmB) Amphotericin B Aprotinin Bacitracin Bictegravir; Emtricitabine; Tenofovir Alafenamide Cisplatin Colchicine; Probenecid Cyclosporine Dapsone Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide
- Doravirine; Lamivudine; Tenofovir disoproxil fumarate Doxorubicin Efavirenz; Emtricitabine; Tenofovir Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate Emtricitabine Emtricitabine; Rilpivirine; Tenofovir alafenamide Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate Emtricitabine; Tenofovir alafenamide Emtricitabine; Tenofovir disoproxil fumarate Entecavir Flucytosine Gentamicin Hyaluronidase, Recombinant; Immune Globulin Hydroxyurea Imipenem; Cilastatin Immune Globulin IV, IVIG, IGIV Kanamycin Lamivudine; Tenofovir Disoproxil Fumarate Mycophenolate Paromomycin Pentamidine Plazomicin Polymyxin B Streptomycin Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole Tacrolimus Talimogene Laherparepvec Telbivudine Tenofovir Alafenamide Tenofovir, PMPA Tobramycin Trimethoprim Vancomycin Vinblastine Vinca alkaloids Vincristine Liposomal Vincristine Vinorelbine Zidovudine
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Valganciclovir2 x 450mg VGCV tablets | Drug | Valganciclovir |
| PlaceboPlacebo equivalent of 900mg/day VGCV | Drug | Placebo |
Primary outcome
White matter integrity of the inferior fronto-occipital fasciculus (IFOF)
Time frame: 8 weeks
Mean fractional anisotropy of the IFOF measured with diffusion tensor imaging
1 secondary outcome
Volume of the medial temporal gyrus (MTG)
Time frame: 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Apr 2026.
- Individual participant dataSharing planned: No
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Valganciclovir in people with Major Depressive Disorder, run by Laureate Institute for Brain Research, Inc. at 1 site 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 11 inclusion and 45 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 21 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
White matter integrity of the inferior fronto-occipital fasciculus (IFOF) (time frame: 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 21 Apr 2026.