Recruiting

L-methylfolate

Sponsor:

Queen's University

Code:

NCT06218030

Conditions

Generalized Anxiety Disorder

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Interventions

L-methylfolate

Study Details

Brief summary:

The goal of this feasibility study is to determine the tolerability and safety of add on treatment with L-methylfolate in patients with treatment-resistant generalized anxiety disorder (GAD). The primary objective is to monitor for side effects and other risks associated with the treatment. Secondary objectives are to compare the severity of symptoms, serum levels of folate, vitamin B12, C-reactive protein, homocysteine, tumor necrosis factor alpha and interleukin 6 before and after treatment. Participants will continue with their usual treatment for GAD and receive add on treatment with L-methylfolate 15 mg per day for 8 weeks. All participants will receive the same intervention.

Conditions

Generalized Anxiety Disorder

Study ID

NCT06218030

Start date

Oct 22, 2024

Status verified date

May, 2025

Completion date

May 1, 2026

Anticipated

Primary completion date

Apr 1, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Adults.
  • Patients on a stable dose of an selective serotonin uptake inhibitors (SSRI) or serotonin and noradrenaline reuptake inhibitors (SNRI) for at least 8 weeks.
  • Treatment-resistant GAD, defined by lack of response to at least two drugs, from two different classes of drugs considered first-line or second-line for GAD according to the Canadian Clinical Practice Guidelines for the Management of Anxiety, Posttraumatic Stress and Obsessive-Compulsive Disorders (Katzman et al., 2014). Only trials lasting at least 8 weeks and with at least the minimum effective dose of the given medication will be considered failed trials.

Exclusion Criteria:

  • Patients with moderate to severe major depressive disorder based on the Patient Health Questionnaire - Nine Item (PHQ-9) scale (score of 15 or above) at baseline.
  • Mini International Neuropsychiatric Interview version (MINI) 7.0 indicates moderate to high current suicidality or "suicide likely in near future" or current suicidal behavior disorder.
  • Patients diagnosed with obsessive-compulsive disorder (OCD), bipolar disorder, schizophrenia, schizoaffective disorder, personality disorders, substance use disorders, intellectual disabilities, dementia, epilepsy or other severe neurological diseases.
  • Patients with cardiovascular diseases, infections, inflammatory diseases, recent surgeries, recent physical trauma and other medical issues that could produce elevation of c-reactive protein (CRP) or homocysteine.
  • Consumption of cannabis, any cannabis by-products, illicit drugs, or alcohol above 3 drinks per week.
  • Supplementation of diet with vitamins or consumption of natural health products that may affect anxiety or depression symptoms.
  • Reading competence below Grade 5.
  • Participants who do not have capacity to conduct consent process.

Study Design

Enrollment

10 participants

Anticipated

Intervention Model

Single group

Primary purpose

Other

Interventions and Outcome Measures

Arms

experimental: L-methylfolate arm

Oral administration of L-methylfolate 15 mg per day for 8 weeks.

Interventions

L-methylfolate

Oral administration of L-methylfolate 15 mg per day for 8 weeks. The study drug will be given in addition to the standard of care (SOC) for GAD.

Primary outcome measure

  • Incidence of treatment-emergent adverse events [ Time Frame: Throughout the study, 8 weeks ]
  • Incidence of treatment-emergent side effects measured with the ASEC [ Time Frame: Baseline visit, 4-week visit and 8-week visit. ]
  • Response to treatment defined by CGI-I score below 3 [ Time Frame: 4-week visit and 8-week visit. ]

Central Contacts and Locations

Locations

Kingston Health Sciences Centre

Recruiting

Kingston, Ontario, Canada, K7L 2V7

Contacts

Yan Deng

+1-613-548-7839yan.deng@queensu.ca

Principal Investigator:

Rafael Freire, MD PhD

More Information

Sponsor

Queen's University

Last update posted

May 25, 2025

Last verified

May, 2025

Keywords

  • generalized anxiety disorder
  • anxiety disorder

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Queen's University on 2025-05-25.