Folate Augmentation of Treatment - Evaluation for Depression: a Randomised Controlled Trial (FolATED)

This study has been completed.
Sponsor:
Collaborators:
NHS Health Technology Assessment Programme
Swansea University
Cardiff University
University of Liverpool
North West Wales NHS Trust
North East Wales NHS Trust
Swansea NHS Trust
Information provided by (Responsible Party):
Bangor University
ClinicalTrials.gov Identifier:
NCT00514410
First received: August 9, 2007
Last updated: October 11, 2011
Last verified: February 2009
  Purpose

To determine whether giving folic acid to people with depression will help their antidepressants work better. If folate does help antidepressants to work better, then it will provide a safe, simple and cheap way of improving the treatment of depression.


Condition Intervention Phase
Depression
Drug: Folic Acid
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Folate Augmentation of Treatment - Evaluation for Depression: a Randomised Controlled Trial

Resource links provided by NLM:


Further study details as provided by Bangor University:

Primary Outcome Measures:
  • Self rated symptoms of depression using the Beck Depression Inventory [ Time Frame: Repeated measures up to 6 months after initiation of folic acid/placebo ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Clinician rated depression using the Montgomery−Asberg Depression Rating Scale [ Time Frame: Repeated measures up to 6 months after initiation of folic acid/placebo ] [ Designated as safety issue: No ]
  • Clinician rated symptom severity using the Clinical Global Impression scale [ Time Frame: Repeated measures up to 6 months after initiation of folic acid/placebo ] [ Designated as safety issue: No ]
  • Health status using the SF12 [ Time Frame: Repeated measures up to 6 months after initiation of folic acid/placebo ] [ Designated as safety issue: No ]
  • Adverse events [ Time Frame: Repeated measures up to 6 months after initiation of folic acid/placebo ] [ Designated as safety issue: Yes ]
  • Cost Utility using the EuroQol, resource use questionnaire and medication history [ Time Frame: Repeated measures up to 6 months after initiation of folic acid/placebo ] [ Designated as safety issue: No ]
  • Folate status [ Time Frame: Baseline, 3 months and 6 months ] [ Designated as safety issue: Yes ]
  • Homocysteine Status [ Time Frame: Baseline, 3 months and 6 months ] [ Designated as safety issue: No ]
  • The interaction between any of the genetic polymorphisms in the folate pathway that predicts the severity of depression, response to antidepressants, and the response to folate supplementation [ Time Frame: Baseline only ] [ Designated as safety issue: No ]
  • Compliance - using the number of tablets remaining at each follow up, dispensing records for folic acid or placebo, dates of repeat prescriptions, Morisky questionnaire, red cell folate and homocysteine levels [ Time Frame: 12 weeks and 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 730
Study Start Date: July 2007
Study Completion Date: May 2011
Primary Completion Date: May 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Folic Acid Drug: Folic Acid
Folic acid 5 mg once a day for three months as a supplement to their antidepressant treatment
Placebo Comparator: Placebo Drug: Placebo
Matching placebo taken once a day for three months

Detailed Description:

Clinical depression is common, debilitating and treatable; one in four people experience it during their lives. The majority of sufferers are treated in primary care and only half respond well to active treatment. Evidence suggests that folate may be a useful adjunct to antidepressant treatment: 1) patients with depression often have a functional folate deficiency; 2) the severity of such deficiency, indicated by elevated homocysteine, correlates with depression severity, 3) low folate is associated with poor antidepressant response, and 4) folate is required for the synthesis of neurotransmitters implicated in the pathogenesis and treatment of depression.

The primary objective of this multi-centred placebo-controlled randomised trial is to estimate the effect of folate augmentation in new or continuing treatment of depressive disorder in primary and secondary care. Secondary objectives are to evaluate the cost-effectiveness of folate augmentation of antidepressant treatment, investigate how the response to antidepressant treatment depends on genetic polymorphisms relevant to folate metabolism and antidepressant response, and explore whether baseline folate status can predict response to antidepressant treatment.

Comparisons: Eligible patients with moderate to severe depression will be randomised to receive 5mg of folic acid or placebo as an adjunct to their antidepressant treatment.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Only patients aged 18 or over
  • ICD-10 diagnosis of moderate to severe depression
  • Able to give informed consent (not delirious, actively psychotic or with severe communication or learning disability)
  • Able to complete the research assessments

Exclusion Criteria:

  • are folate deficient
  • are B12 deficient
  • have knowingly taken supplements containing folic acid within 2 months
  • suffer from psychosis
  • are already participating in another research project
  • are pregnant or planning to become pregnant
  • are taking anticonvulsants
  • have a serious, advanced or terminal illness with a life expectancy of less than 1 year
  • have recently started treatment for a medical condition which has not yet been stabilised
  • are taking lithium
  • have had a diagnosis or treatment for any malignant disease or any related condition such as intestinal polyposis
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00514410

Locations
United Kingdom
North West Wales Trust
Bangor, Gwynedd, United Kingdom, LL57 2PW
Swansea University
Swansea, United Kingdom, SA2 8PP
Cardiff University
Wrexham, United Kingdom, LL13 7YP
Sponsors and Collaborators
Bangor University
NHS Health Technology Assessment Programme
Swansea University
Cardiff University
University of Liverpool
North West Wales NHS Trust
North East Wales NHS Trust
Swansea NHS Trust
Investigators
Principal Investigator: Ian T Russell, PhD, HonFRCGP, FRCP Edin, FFPH Swansea University
Principal Investigator: Keith Lloyd, MBBS, MSc, MRC Psych, MSc, MD Swansea University
  More Information

Additional Information:
Publications:
Responsible Party: Bangor University
ClinicalTrials.gov Identifier: NCT00514410     History of Changes
Other Study ID Numbers: G0373, ISRCTN37558856
Study First Received: August 9, 2007
Last Updated: October 11, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Bangor University:
Depression
Folate
Folic acid
Antidepressants

Additional relevant MeSH terms:
Depression
Depressive Disorder
Behavioral Symptoms
Mood Disorders
Mental Disorders
Antidepressive Agents
Folic Acid
Vitamin B Complex
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Hematinics
Hematologic Agents
Vitamins
Micronutrients
Growth Substances
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 26, 2014