- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04724447
ANTIVIRAL TREATMENT OF CYTOMEGALOVIRUS IN DEPRESSION
EXPERIMENTAL ANTIVIRAL TREATMENT OF CYTOMEGALOVIRUS IN DEPRESSION: AFFECTIVE, NEURAL, AND INFLAMMATORY MECHANISMS
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Estimated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Jonathan Savitz, PhD
- Phone Number: 918 502 5104
- Email: jsavitz@laureateinstitute.org
Study Locations
-
-
Oklahoma
-
Tulsa, Oklahoma, United States, 74136
- Recruiting
- Laureate Institute for Brain Research
-
Contact:
- Jonathan Savitz, PhD
- Phone Number: 918-502-5104
- Email: jsavitz@laureateinstitute.org
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
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.
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Valganciclovir
900 milligrams (mg) valganciclovir (VGCV) to be taken orally once per day for 8 weeks.
|
2 x 450mg VGCV tablets
|
Placebo Comparator: Placebo
Placebo equivalent of 900 milligrams (mg) VGCV to be taken orally once per day for 8 weeks.
|
Placebo equivalent of 900mg/day VGCV
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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
|
8 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Volume of the medial temporal gyrus (MTG)
Time Frame: 8 weeks
|
Mean gray matter volume of the MTG measured with structural MRI
|
8 weeks
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Volume of the orbitofrontal cortex (OFC)
Time Frame: 8 weeks
|
Mean gray matter volume of the OFC measured with structural MRI
|
8 weeks
|
Inflammatory mediators
Time Frame: 8 weeks
|
Serum concentration of inflammatory mediators: CXCL10, sCD14, and TNF measured with ELISA or the Mesoscale Discovery Platform
|
8 weeks
|
CD8+ cells
Time Frame: 8 weeks
|
Percentage of terminally differentiated CD8+ cells (TEMRA cells) measured with flow cytometry
|
8 weeks
|
Anhedonia
Time Frame: 8 weeks
|
Symptoms of anhedonia measured with the Snaith-Hamilton Pleasure Scale (SHAPS).
Higher scores are indicative of greater anhedonia.
|
8 weeks
|
Depression
Time Frame: 8 weeks
|
Symptoms of depression measured with the Montgomery-Asberg Depression Rating Scale (MADRS).
Higher scores are indicative of more severe depression.
|
8 weeks
|
Collaborators and Investigators
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2021-001
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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