Major Depressive Disorder (MDD), Pediatrics, Thiamine, Thiamine Diphosphate (TDP), Vitamin B1
Conditions
Keywords
Major Depressive Disorder (MDD), Thiamine, Vitamin B1, Pediatrics, Thiamine Diphosphate (TDP)
Brief summary
The goal of this study is to examine the effectiveness of thiamine in reducing depressive symptoms in children and adolescents. The investigators hypothesize that thiamine administration will alleviate depressive symptoms in children and adolescents and will have a favorable safety profile. Participants will complete a baseline virtual visit with a study clinician and parent/guardian questionnaires to assess depression symptoms, medical history, current medications, and study eligibility. Participants will complete fasting blood draws before and after the 4-week study period and, if eligible, receive study thiamine capsules by mail to take daily during the study. Participants will attend weekly virtual visits for 4 weeks to monitor depression symptoms, safety, medication adherence, side effects, and any changes in medications or treatments.
Detailed description
This will be a 28-day, open-label, Phase 2a pilot trial to evaluate the efficacy and safety of 100 mg of daily oral thiamine in the treatment of depression in children and adolescents. Subjects will include pediatric patients 8-17 years of age with elevated depressive symptoms. The investigators plan to enroll 40 subjects to account for an expected dropout rate, with the goal of retaining 30 participants for analysis. The main outcome measures will be improvement in depressive symptoms as measured by the Children Depression Rating Scale-Revised (CDRS-R). Overall clinical functioning will be assessed using the Clinical Global Impression of Severity (CGI-S) and Improvement (CGI-I) scales. The Children's Depression Inventory-2 Parent Form (CDI-2) will also be included as a secondary outcome measure. Thiamine status will be assessed by measuring thiamine diphosphate (TDP) concentrations in whole blood samples (3 mL), collected in EDTA tubes (lavender top) at two time points: at baseline and at the end of study (Day 28). In addition to measuring thiamine diphosphate (TDP) concentrations, the investigators will also assess a panel of inflammatory and metabolic biomarkers at baseline and at the end of study (Day 28). These biomarkers include C-reactive protein (CRP), tumor-necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and leptin. Biomarker testing allows exploration of potential thiamine mechanisms of action. The investigators plan to treat subjects with the following doses: Thiamine hydrochloride (HCL): 100 mg daily At each visit, measures of safety and efficacy will be obtained using rating scales.
Interventions
Participants will receive 100 mg HCl oral thiamine capsules, which will be swallowed whole.
Sponsors
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
This will be a 28-day, open-label, Phase 2a pilot trial to evaluate the efficacy and safety of 100 mg of daily oral thiamine in the treatment of depression in children and adolescents.
Eligibility
Sex/Gender
ALL
Age
8 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* Male or female participants aged 8 to 17.5 years (inclusive) at the time of enrollment * Diagnosis of major depressive disorder (MDD) according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) * Evidence of clinically significant symptoms of depression as indicated by a T score\> 60 on the Children's Depression Inventory 2 (CDI-2) parent form at prescreening * Evidence of clinically significant symptoms of depression in the mild to moderate range as indicated by a score between 40 and 70 on the Children's Depression Rating Scale--Revised (CDRS-R) at screening * Subjects and their caregivers must be English-speaking and have a level of understanding sufficient to communicate intelligently with the investigator and study coordinator, and to cooperate with all tests and examinations required by the protocol. * Subject and their caregiver must be willing and able to comply with all study procedures. * Each subject and his/her authorized parent/guardian must understand the nature of the study. The subject's authorized parent/guardian must sign an informed consent document, and the subject must sign an informed assent document. * Subject must be able to swallow pills. * Subject must have access to a computer with a camera, speaker, microphone, and internet connection. * Subjects must be willing to refrain from treatment changes during the study protocol.
Exclusion criteria
* Recent history or active clinically significant manifestations of infectious, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular, gastrointestinal, musculoskeletal, dermatological, urogenital, neurological, endocrinological or eyes, ears, nose, and throat disorders, or any other acute or chronic condition that, in the Investigator's opinion, would limit the participant's ability to complete or participate in this clinical study. * History of sensitivity to thiamine * Severe allergies or multiple adverse drug reactions. * History of nutritional deficiencies other than thiamine deficiency that could interfere with the study protocol or confound results. * DSM-V diagnosis of substance use disorder, abuse or dependence. * Judged clinically to be at serious suicidal risk for Columbia-Suicide Severity Rating Scale (C-SSRS) score ≥4. * Severe symptoms of depression as indicated by CDRS-R score \>70. * Current diagnosis of bipolar disorder. * Current diagnosis of schizophrenia. * Current diagnosis or symptoms of psychosis. * Previous or current diagnosis of Intellectual Disability. * Participants who are on stable pharmacotherapy will be included as long as the medication has been stable for at least 6 weeks prior to screening and will continue without change for the duration of the study. Participants on pharmacotherapy that has not been stable for at least 6 weeks will be excluded. * Participants who are in stable psychotherapy will be included as long as they have started psychotherapy at least 3 months prior to screening and will continue therapy without change for the duration of the study. Participants receiving psychotherapy that has not been stable for at least 6 weeks will be excluded. * Concomitant treatment or treatment within the last month with neuroleptics, antipsychotics, anticonvulsants, sedatives or hypnotics. * More than two antidepressant treatment failures at an adequate dose and duration (at least 6 weeks) in the current major depressive episode. * Having started psychotherapy (including cognitive behavioral therapy \[CBT\]) less than 3 months prior to Screening * Pregnancy: Female participants who are pregnant or breastfeeding will be excluded to avoid risks to the child and ensure safety in the use of thiamine.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Children's Depression Rating Scale-Revised (CDRS-R) Total Score | 28 days | Change in depressive symptom severity from baseline to Week 4 as measured by the Children's Depression Rating Scale-Revised (CDRS-R). Lower scores indicate reduced depression severity and improvement in depressive symptoms over the course of thiamine treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Demonstrating Clinical Improvement on the Clinical Global Impressions-Improvement (CGI-I) Scale | 28 days | Number of participants demonstrating clinical improvement on the Clinical Global Impressions-Improvement (CGI-I) Scale at Week 4. The proportion of participants meeting the predefined improvement threshold will be reported along with the corresponding 95% confidence interval. |
Contacts
CONTACTClotilde Guidetti, MD
Outcome results
None listed