Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT06218030
Other study ID # 6038351
Secondary ID
Status Not yet recruiting
Phase Phase 4
First received
Last updated
Start date April 2024
Est. completion date March 2025

Study information

Verified date January 2024
Source Queen's University
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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 and homocysteine 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.


Description:

Background: Up to 33.7% of the population are affected by an anxiety disorder during their lifetime according to large populationbased surveys. Generalized anxiety disorder (GAD) has a lifetime prevalence of 2.8% to 6.2% in these studies. GAD is associated with functional, occupational, and quality of life impairments. Certain types of medications and psychotherapies are established treatments for GAD, but only 50% of the patients respond to the first treatment trial. Deficiency of folates and neuroinflammation are two hypothesis that could explain why some patients with anxiety disorders do not respond to the usual treatments. Supplementation with folates could correct these deficiencies and reduce inflammation, thus increasing the success rates for treatments. In studies with major depressive disorder, adjunctive folates were associated to higher remission rates. Other studies indicate that folate supplementation lowers homocysteine levels and inflammation. Objectives: Ascertain if adjunctive treatment with Lmethylfolate can produce improvement in treatment-resistant GAD subjects. Methods: This is a proof-of-concept pilot study, an open-label trial of adjunctive treatment with L-methylfolate in patients with treatment-resistant GAD. Ten adult patients with treatment-resistant GAD who have been on a stable dose of an SSRI or SNRI for at least 12 weeks will receive 15 mg doses of L-methylfolate daily for 8 weeks. Patients with moderate to severe major depressive disorder or suicide risk will not be included. Serum levels of folate, vitamin B12, C-reactive protein and homocysteine will be measured before and after the trial.


Recruitment information / eligibility

Status Not yet recruiting
Enrollment 10
Est. completion date March 2025
Est. primary completion date March 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years to 65 Years
Eligibility 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


Related Conditions & MeSH terms


Intervention

Drug:
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.

Locations

Country Name City State
Canada Kingston Health Sciences Centre Kingston Ontario

Sponsors (1)

Lead Sponsor Collaborator
Queen's University

Country where clinical trial is conducted

Canada, 

References & Publications (3)

Miller AL. The methylation, neurotransmitter, and antioxidant connections between folate and depression. Altern Med Rev. 2008 Sep;13(3):216-26. — View Citation

Saraswathy KN, Ansari SN, Kaur G, Joshi PC, Chandel S. Association of vitamin B12 mediated hyperhomocysteinemia with depression and anxiety disorder: A cross-sectional study among Bhil indigenous population of India. Clin Nutr ESPEN. 2019 Apr;30:199-203. doi: 10.1016/j.clnesp.2019.01.009. Epub 2019 Feb 12. — View Citation

Taylor MJ, Carney SM, Goodwin GM, Geddes JR. Folate for depressive disorders: systematic review and meta-analysis of randomized controlled trials. J Psychopharmacol. 2004 Jun;18(2):251-6. doi: 10.1177/0269881104042630. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Incidence of treatment-emergent adverse events Monitor participants for treatment-emergent adverse events and serious adverse events. Throughout the study, 8 weeks
Primary Incidence of treatment-emergent side effects measured with the ASEC Monitor participants for minor treatment-emergent side effects measured with the Antidepressant Side-Effect Checklist (ASEC).
ASEC is a list of 21 possible side effects from antidepressants. Each item is rated from 0 (absent) to 3 (severe).
Baseline visit, 4-week visit and 8-week visit.
Primary Response to treatment defined by CGI-I score below 3 Response to treatment, which will be defined as a score of 1 or 2 on the Clinical Global Impression - Improvement (CGI-I) scale.
CGI-I is a clinician administered one-item clinical scale rated from 1 (very much improved) to 7 (very much worse). Not assessed would confer score 0.
4-week visit and 8-week visit.
Secondary Remission defined by CGI-S score below 3 Remission will be defined as a score of 1 or 2 on the Clinical Global Impression - Severity (CGI-S) scale.
CGI-S is a clinician administered one-item clinical scale rated from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Not assessed would confer score 0.
4-week visit and 8-week visit.
Secondary Change in anxiety severity measured by CGI-S Changes in scores for CGI-S by comparing the scores in each visit. CGI-S is a clinician administered one-item clinical scale rated from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). Not assessed would confer score 0. Baseline visit, 4-week visit and 8-week visit.
Secondary Change of anxiety symptoms measured with GAD-7 Changes in scores for Generalized Anxiety Disorder 7-item scale (GAD-7) by comparing the scores in each visit.
GAD-7 is a self-rated 7-item scale, each item is rated from 0 (not at all) to 3 (nearly every day).
Baseline visit, 4-week visit and 8-week visit.
Secondary Change of anxiety symptoms measured with PSWQ Changes in scores for Penn State Worry Questionnaire (PSWQ) by comparing the scores in each visit.
PSWQ is a self-rated 16-item scale, each item is rated from 1 (not at all typical of me) to 5 (very typical of me).
Baseline visit, 4-week visit and 8-week visit.
Secondary Change of anxiety symptoms measured with BAI Changes in scores for Beck Anxiety Inventory (BAI) by comparing the scores in each visit.
BAI is a self-rated 21-item scale, each item is rated from 0 (not at all) to 3 (severely - it bothered me a lot).
Baseline visit, 4-week visit and 8-week visit.
Secondary Concentration of CRP in serum Collection of blood sample and measurement of the concentration of C-Reactive Protein (CRP) in serum. Baseline visit and 8-week visit.
Secondary Concentration of homocysteine in serum Collection of blood sample and measurement of the concentration of homocysteine in serum. Baseline visit and 8-week visit.
Secondary Concentration of vitamin B12 in serum Collection of blood sample and measurement of the concentration of vitamin B12 in serum. Baseline visit and 8-week visit.
Secondary Concentration of folate in serum Collection of blood sample and measurement of the concentration of folate in serum. Baseline visit and 8-week visit.
See also
  Status Clinical Trial Phase
Terminated NCT03420456 - Transcranial Pulse Near-Infrared Light in Generalized Anxiety Disorder: a Placebo-Controlled Study N/A
Active, not recruiting NCT05530642 - An Augmented Training Program for Preventing Post-Traumatic Stress Injuries Among Diverse Public Safety Personnel N/A
Withdrawn NCT02382224 - Worry Exposure for Generalized Anxiety Disorder N/A
Completed NCT02306356 - Internet-delivered Treatment for Children With Anxiety Disorders in a Rural Area; an Open Trial in a Clinical Setting N/A
Completed NCT02256566 - Cognitive Training for Mood and Anxiety Disorders N/A
Completed NCT01958788 - Testing Beliefs About Uncertainty in the Treatment of Generalized Anxiety Disorder N/A
Completed NCT01681329 - Cognitive-Behavioral Treatment and Interpretation Modification Training for Adults With Generalized Anxiety Disorder N/A
Completed NCT01337713 - Efficacy of Massage Therapy in the Treatment of Generalized Anxiety Disorder (GAD) N/A
Completed NCT01201967 - A Collaborative Care Program to Improve Treatment of Depression and Anxiety Disorders in Cardiac Patients Phase 4
Completed NCT01342120 - PHARMO Institute Seroquel Safety Study N/A
Completed NCT00961298 - An Open Label Trial of Duloxetine in the Treatment of Irritable Bowel Syndrome and Comorbid Generalized Anxiety Disorder Phase 4
Completed NCT01203293 - Cognitive Behavioral Therapy (CBT) for Latinos With Generalized Anxiety Disorder in the General Medical Sector Phase 1
Completed NCT01971203 - Efficacy of Extended-release Quetiapine (Seroquel XR) as Adjunctive Therapy to Cognitive Behavioral Therapy in the Treat N/A
Terminated NCT01244711 - Open-Label Pilot Study to Examine the Value of Substituting Quetiapine for Benzodiazepines Phase 4
Completed NCT00744627 - Efficacy and Safety of Vortioxetine (Lu AA21004) for Treatment of Generalized Anxiety Disorder in Adults. Phase 3
Completed NCT00711737 - Study of the Changes in Metabolic Parameters in Patients Treated With Escitalopram for Six Months N/A
Completed NCT00515242 - Therapeutic Massage for Generalized Anxiety Disorder Phase 1/Phase 2
Completed NCT00537615 - An Open-label Study to Investigate the Absorption, Metabolism and Excretion of Radiolabeled PD 0332334 in Six Healthy Male Volunteers Phase 1
Completed NCT00525226 - Evaluating the Effects of Stress in Pregnancy N/A
Completed NCT00620776 - Combined Treatment for Generalized Anxiety Disorder (GAD) Phase 2