Ignite Creation Date:
2024-05-05 @ 5:27 PM
Last Modification Date:
2024-10-26 @ 9:32 AM
Study NCT ID:
NCT00459264
Status:
COMPLETED
Last Update Posted:
2016-11-23
First Post:
2007-04-10
Brief Title:
Prevention of Mood Disorders by Folic Acid Supplementation
Sponsor:
University of Oxford
Organization:
University of Oxford
Study Overview
Official Title:
Prevention of Mood Disorders by Folic Acid Supplementation
Status:
COMPLETED
Status Verified Date:
2016-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PRE-EMPT
Brief Summary:
The purpose of this study is to determine whether daily folic acid supplements can prevent new episodes of mood disorder in young people aged 14-24 years of biological parents with current or past history of depression or bipolar disorder
Detailed Description:
Bipolar disorder and recurrent major depression are life-long disabling illnesses that often first become clinically apparent in the late teenage years or early twenties People who develop clinical mood disorders characteristically have milder short-lived symptoms of mood disturbance prior to the onset of clinical illness These sub-clinical disturbances represent a risk factor for the subsequent development of clinical disorders Angst 2000 Aalto-Setala 2002 A number of physiological abnormalities associated with depression persist after symptom resolution suggesting that depression may cause a kind of biological scarring of the brain that can predispose to further episodes of illness
Nutritional supplements are a feasible intervention for primary prevention because they are likely to be acceptable and intuitively would seem to have a greater chance of being effective at a preventative stage rather than later when disease progression has occurred
Folate and mood disturbance
Low plasma and red cell folate have long been associated with clinical depressive disorders and treatment with folic acid 500mcg daily has been shown to improve the therapeutic effect of fluoxetine in depressed patients see Coppen and Bailey 2000 A growing number of epidemiological studies also suggest links between low folate status increased homocysteine and depressive symptomatology in the general population Tiemeier et al 2002 Bjelland et al 2003 Morris et al 2003
Objectives
Primary
To determine whether folic acid supplementation can prevent new episodes of mood disorder in teenage children of parents with recurrent depression or bipolar disorder
Secondary
To determine whether folic acid supplementation can improve depression scores on the Mood and Feeling Questionnaire in teenage children of parents with recurrent depression or bipolar disorder
To determine whether folic acid supplementation can improve scores on the Altman Mania Rating Scale in teenage children of parents with recurrent depression or bipolar disorder
To determine whether there is a correlation between genotypes for folate enzymes and response to folate
Endpoints
Primary
Occurrence of an episode of Axis 1 mood disorder on DSM-IV as determined by the Structured Clinical Interview for DSM-IV SCID
Secondary
Change in Score on The Mood and Feeling Questionnaire
Change in score on the Altman Mania Rating Scale
Correlation between genotypes for folate enzymes and response to folate
Study design
This will be a randomized concealed allocation placebo-controlled study with masking of participants and investigators Participants will initially enter a 4 week run-in phase during which they take folic acid 25mg If consent and compliance are maintained during the active run-in participants with then be randomised to one of two treatments in a parallel group design a Folic acid 25mg daily or b identical placebo liquid A web-based algorithm will be used which will be accessed by researchers either online or by phone call to the study office Access to the randomisation code will be limited to the trial programmer with temporary access given to another member of the trial team during her absence The treatment period will be thirty six months
PRE-EMPT will continue screening until there are 200 teenagers in the randomised phase male and female 14-24 years of age who have a biological parent with a life-time history of recurrent major depression bipolar I or bipolar II disorder Family history will be assessed using proband questions Subjects will be excluded if they have any current or past DSM-IV Axis I disorder This will be assessed using the Structured Clinical Interview for DSM-IV SCID Current or past sub-syndromal mood and anxiety disorder will not be a reason for exclusion but will be assessed and used in the minimization processWe will also exclude subjects with a significant on-going medical condition particularly epilepsy or those who are already using folate supplements and who are unwilling to give them up for the duration of the study All subjects will give informed written consent to the study and a parent or guardian will also give written consent where subjects are under 16 years of age Minimization will be carried out for age gender family history and the presence of sub-syndromal mood disturbance to ensure balanced treatment allocation
Ratings and follow-up On entry to the study subjects will complete ten self-rating instruments the Mood and Feeling Questionnaire MFQ a 32-item scale designed to detect and monitor adolescent depression in the community Cooper and Goodyer 1993 Wood et al 1995 Subjects will also complete the Altman Mania Rating Scale a 5-item scale designed to mania Altman et al 1997 the Insomnia Severity Index ISI a 5-item scale designed to detect the severity of insomnia Morin 1993 and the Hospital Anxiety and Depression Scale HADS a 14 item scale to determine anxiety and depression Zigmond and Snaith 1983 Subsequently subjects will complete the MFQ Altman ISI and HADS monthly We will have available both web-based assessments and written forms whichever the participant prefers The other rating scales to be completed on entry are the Cambridge Life Events Rating Scale CLE Eysenck Personality Questionnaire EPQ Response Styles Questionnaire RSQ Parental Bonding Inventory PBI Childrens Attributional Style Questionnaire CAS and the Morningness-Eveningness Questionnaire MEQ
At six monthly intervals subjects will be re-interviewed with the SCID to assess whether they have met criteria for any DSM-IV Axis I disorder in the preceding six months The CLE and CAS will also be repeated at six monthly intervals
Prior to entry to the investigation we ask subjects to provide a blood sample for the following
1 Full blood count Red cell folate B12 homocysteine levels
2 DNA sample for polymorphisms of the proteins involved in folate metabolism and related neurotransmitters
These measures apart from the DNA analysis will be repeated annually
Prior to entry we also wish to assess waking salivary cortisol In a separate study we have found that healthy young people with a parent who has a history of mood disorder ie the same participant population that we are recruiting for this study have elevated waking levels of salivary cortisol relative to controlsThe measurement of waking salivary cortisol is a simple non-invasive test which may represent a marker of vulnerability to depression If this is the case it might be altered by folate treatment which we are using in the present study to decrease the risk of depression
We therefore propose to ask subjects to take a sample of waking salivary cortisol before they begin folateplacebo treatment and again after about six months in the study In this way we will be able to assess the effect of folateplacebo treatment on waking salivary cortisol The eventual aim will be assess whether relative to placebo folic acid treatment lowers waking salivary cortisol and whether this is associated with decreased risk of depression
From the point of view of storage and custody the saliva samples will be treated exactly as the blood samples taken for folate estimation
Nutritional supplements are a feasible intervention for primary prevention because they are likely to be acceptable and intuitively would seem to have a greater chance of being effective at a preventative stage rather than later when disease progression has occurred
Folate and mood disturbance
Low plasma and red cell folate have long been associated with clinical depressive disorders and treatment with folic acid 500mcg daily has been shown to improve the therapeutic effect of fluoxetine in depressed patients see Coppen and Bailey 2000 A growing number of epidemiological studies also suggest links between low folate status increased homocysteine and depressive symptomatology in the general population Tiemeier et al 2002 Bjelland et al 2003 Morris et al 2003
Objectives
Primary
To determine whether folic acid supplementation can prevent new episodes of mood disorder in teenage children of parents with recurrent depression or bipolar disorder
Secondary
To determine whether folic acid supplementation can improve depression scores on the Mood and Feeling Questionnaire in teenage children of parents with recurrent depression or bipolar disorder
To determine whether folic acid supplementation can improve scores on the Altman Mania Rating Scale in teenage children of parents with recurrent depression or bipolar disorder
To determine whether there is a correlation between genotypes for folate enzymes and response to folate
Endpoints
Primary
Occurrence of an episode of Axis 1 mood disorder on DSM-IV as determined by the Structured Clinical Interview for DSM-IV SCID
Secondary
Change in Score on The Mood and Feeling Questionnaire
Change in score on the Altman Mania Rating Scale
Correlation between genotypes for folate enzymes and response to folate
Study design
This will be a randomized concealed allocation placebo-controlled study with masking of participants and investigators Participants will initially enter a 4 week run-in phase during which they take folic acid 25mg If consent and compliance are maintained during the active run-in participants with then be randomised to one of two treatments in a parallel group design a Folic acid 25mg daily or b identical placebo liquid A web-based algorithm will be used which will be accessed by researchers either online or by phone call to the study office Access to the randomisation code will be limited to the trial programmer with temporary access given to another member of the trial team during her absence The treatment period will be thirty six months
PRE-EMPT will continue screening until there are 200 teenagers in the randomised phase male and female 14-24 years of age who have a biological parent with a life-time history of recurrent major depression bipolar I or bipolar II disorder Family history will be assessed using proband questions Subjects will be excluded if they have any current or past DSM-IV Axis I disorder This will be assessed using the Structured Clinical Interview for DSM-IV SCID Current or past sub-syndromal mood and anxiety disorder will not be a reason for exclusion but will be assessed and used in the minimization processWe will also exclude subjects with a significant on-going medical condition particularly epilepsy or those who are already using folate supplements and who are unwilling to give them up for the duration of the study All subjects will give informed written consent to the study and a parent or guardian will also give written consent where subjects are under 16 years of age Minimization will be carried out for age gender family history and the presence of sub-syndromal mood disturbance to ensure balanced treatment allocation
Ratings and follow-up On entry to the study subjects will complete ten self-rating instruments the Mood and Feeling Questionnaire MFQ a 32-item scale designed to detect and monitor adolescent depression in the community Cooper and Goodyer 1993 Wood et al 1995 Subjects will also complete the Altman Mania Rating Scale a 5-item scale designed to mania Altman et al 1997 the Insomnia Severity Index ISI a 5-item scale designed to detect the severity of insomnia Morin 1993 and the Hospital Anxiety and Depression Scale HADS a 14 item scale to determine anxiety and depression Zigmond and Snaith 1983 Subsequently subjects will complete the MFQ Altman ISI and HADS monthly We will have available both web-based assessments and written forms whichever the participant prefers The other rating scales to be completed on entry are the Cambridge Life Events Rating Scale CLE Eysenck Personality Questionnaire EPQ Response Styles Questionnaire RSQ Parental Bonding Inventory PBI Childrens Attributional Style Questionnaire CAS and the Morningness-Eveningness Questionnaire MEQ
At six monthly intervals subjects will be re-interviewed with the SCID to assess whether they have met criteria for any DSM-IV Axis I disorder in the preceding six months The CLE and CAS will also be repeated at six monthly intervals
Prior to entry to the investigation we ask subjects to provide a blood sample for the following
1 Full blood count Red cell folate B12 homocysteine levels
2 DNA sample for polymorphisms of the proteins involved in folate metabolism and related neurotransmitters
These measures apart from the DNA analysis will be repeated annually
Prior to entry we also wish to assess waking salivary cortisol In a separate study we have found that healthy young people with a parent who has a history of mood disorder ie the same participant population that we are recruiting for this study have elevated waking levels of salivary cortisol relative to controlsThe measurement of waking salivary cortisol is a simple non-invasive test which may represent a marker of vulnerability to depression If this is the case it might be altered by folate treatment which we are using in the present study to decrease the risk of depression
We therefore propose to ask subjects to take a sample of waking salivary cortisol before they begin folateplacebo treatment and again after about six months in the study In this way we will be able to assess the effect of folateplacebo treatment on waking salivary cortisol The eventual aim will be assess whether relative to placebo folic acid treatment lowers waking salivary cortisol and whether this is associated with decreased risk of depression
From the point of view of storage and custody the saliva samples will be treated exactly as the blood samples taken for folate estimation
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| 215840206001-0001 | None | None | None |
| 04T-496 | None | None | None |
| 2004-003341-40 | None | None | None |