Anorexia Nervosa, Anxiety
Conditions
Keywords
Anxiety, Anorexia nervosa, Adolescents, Fish oil
Brief summary
Adolescents with anorexia nervosa frequently have associated anxiety, and standard medications used for anxiety are unhelpful when patients are malnourished. This is a 12 week trial examining the safety, tolerability, and effectiveness of fish oil nutritional supplements for anxiety in adolescents with anorexia nervosa.
Detailed description
Anorexia nervosa (AN) is an eating disorder characterized by a morbid fear of weight gain and a perception of being overweight despite objective evidence of weight loss and malnutrition. It has been estimated that almost 0.9% of women will suffer from AN at some point in their lives, and most cases of AN arise during adolescence. Even with appropriate treatment, only about half of patients with AN will have a full recovery, 30% partial recovery, and 20% will progress to having a chronic illness. Earlier, more aggressive treatment with appropriate nutritional recovery during adolescence offers the best chance of a full recovery. Treatment of AN is complicated by the high rate of comorbid psychiatric diagnoses, the physical and cognitive effects of the attendant malnutrition, and the lack of effective pharmacologic interventions. Approximately 75% of patients with AN have a comorbid psychiatric illness, including depression, obsessive compulsive disorder, and anxiety. Anxiety disorders in particular share attributes with AN, including perfectionism, rigidity, compulsivity, and harm avoidance in addition to trait anxiety. Complicating treatment, the risk and severity of patients' anxiety is enhanced by a lower body mass index (BMI), and this low BMI is the likely reason why standard medication treatments for generalized anxiety, such as selective serotonin reuptake inhibitors are ineffective. In order to address these treatment challenges, we propose to study the tolerability, feasibility and efficacy of a non-pharmacologic interventions for anxiety in adolescents with AN: omega-3 polyunsaturated fatty acid (PUFA) supplementation. Over the past 15 years, there has been an interest in possible associations between fish oil and affective illness, particularly depression. Low plasma levels of docosahexaenoic acid, an essential fatty acid found in fish oil, are associated with low concentrations of cerebrospinal fluid 5-hydroxyindolacetic acid (5-HIAA), a marker of central nervous system serotonin turnover. Epidemiologically, those populations with higher fish oil consumption tend to have lower rates of depression, and reported low levels of fish consumption have been associated with a greater risk of depression in women. It has been hypothesized that omega-3 PUFAs alter brain phospholipid composition and enhance membrane fluidity, and this is supported by evidence that supplementation with omega-3 PUFAs decreases brain water proton transverse relaxation times in patients with bipolar disorder. The association with depression and the proposed mechanism of action elicited some interest regarding associations between omega-3 PUFAs and anxiety disorders. Supplementation trials have shown mixed results, with no effects for obsessive compulsive disorder in patients taking maximum doses of selective serotonin reuptake inhibitors, and another showing decreased anxiety symptoms in 22 patients enrolled in a substance abuse treatment program. Recently, Kiecolt-Glaser and colleagues described a decrease in test-related anxiety symptoms in a non-clinical sample of medical students related to supplementation with omega-3 PUFAs. Although there has been some interest in the use of omega-3 PUFA supplementation as an adjunctive treatment for anorexia nervosa, there have been no systematic trials.
Interventions
DRUGFish oil
Participants will take 4 capsules daily
DRUGPlacebo pill
Participants will take 4 capsules daily
Sponsors
Andrea Bonny
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
12 Years to 21 Years
Healthy volunteers
No
Inclusion criteria
Females admitted to Nationwide Children's Hospital Eating Disorder Partial Hospitalization Program
Exclusion criteria
1. Inability to take pills 2. Co-morbid medical conditions affecting appetite and weight (e.g., inflammatory bowel disease, cancer, cystic fibrosis) 3. Co-morbid psychiatric conditions affecting appetite and weight (e.g., bipolar disorder, substance abuse) 4. Currently taking fish oil supplements 5. Inability to participate in study for 12 consecutive weeks.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Medication Side Effects Score | 6 and12 weeks | At 6 and 12 weeks, medication tolerability was assessed via self-report of nine potential side effects (e.g. diarrhea, burping). Participants were asked whether they experienced these side effects never, rarely, occasionally, frequently, or very frequently. Individual responses were assigned a numeric equivalent from 0 to 4, and summed for a total side effect score ranging from 0 to 36. Higher scores indicated greater frequency of side effects and lower medication tolerability. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Beck Anxiety Inventory-Trait (BAIT) | Baseline, 6 weeks, and 12 weeks | The BAIT is a 21-item self-report measure of anxiety severity rated on a 4-point Likert scale (0= rarely or never; 3= almost always). It has shown acceptable reliability and validity in an adolescent psychiatric inpatient population. BAIT scores over 26 indicate severe anxiety, scores 16-25 indicate moderate anxiety, scores 8-15 indicate mild anxiety, and scores 0-7 indicate a minimal level of anxiety. We chose to measure trait anxiety to examine beyond meal-related (state) anxiety. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participant Tolerating Saliva Collection and 24 Hour Heart Rate Monitor Use | Baseline, 6 weeks, and 12 weeks | At baseline, 6 weeks, and 12 weeks, study participants were asked to collect salivary samples 5 times over a 24 hour period. In addition, participants were asked to wear a 24 hour heart monitor during this same 24 hour interval. Compliance wtth completion of these physiological measures was assessed as follows: 1. For saliva collection, compliance was assessed by return of 5 full vials of saliva with record of time collected. 2. For 24 hour heart rate monitor, compliance was assessed by return of monitor with then downloading of data to confirm that the participant wore the device during the specified time interval. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| PUFA Participants randomized to omega-3 PUFA | 12 |
| Placebo Participants randomized to placebo | 12 |
| Total | 24 |
Baseline characteristics
| Characteristic | Total | PUFA | Placebo |
|---|---|---|---|
| Age, Continuous | 14.7 years STANDARD_DEVIATION 1.6 | 15.0 years STANDARD_DEVIATION 1.3 | 14.4 years STANDARD_DEVIATION 1.8 |
| BMI | 19.2 kg/m^2 STANDARD_DEVIATION 2.1 | 19.6 kg/m^2 STANDARD_DEVIATION 2 | 18.8 kg/m^2 STANDARD_DEVIATION 2.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 22 Participants | 12 Participants | 10 Participants |
| Sex: Female, Male Female | 24 Participants | 12 Participants | 12 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 12 |
| other Total, other adverse events | 3 / 12 | 2 / 12 |
| serious Total, serious adverse events | 0 / 12 | 0 / 12 |
Outcome results
Primary
Medication Side Effects Score
At 6 and 12 weeks, medication tolerability was assessed via self-report of nine potential side effects (e.g. diarrhea, burping). Participants were asked whether they experienced these side effects never, rarely, occasionally, frequently, or very frequently. Individual responses were assigned a numeric equivalent from 0 to 4, and summed for a total side effect score ranging from 0 to 36. Higher scores indicated greater frequency of side effects and lower medication tolerability.
Time frame: 6 and12 weeks
Population: Participants who completed at least a baseline study visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PUFA | Medication Side Effects Score | 6 Weeks | 9.5 Score on a scale | Standard Error 1.7 |
| PUFA | Medication Side Effects Score | 12 Weeks | 6.4 Score on a scale | Standard Error 1.8 |
| Placebo | Medication Side Effects Score | 6 Weeks | 6.2 Score on a scale | Standard Error 2 |
| Placebo | Medication Side Effects Score | 12 Weeks | 4.1 Score on a scale | Standard Error 2 |
Secondary
Beck Anxiety Inventory-Trait (BAIT)
The BAIT is a 21-item self-report measure of anxiety severity rated on a 4-point Likert scale (0= rarely or never; 3= almost always). It has shown acceptable reliability and validity in an adolescent psychiatric inpatient population. BAIT scores over 26 indicate severe anxiety, scores 16-25 indicate moderate anxiety, scores 8-15 indicate mild anxiety, and scores 0-7 indicate a minimal level of anxiety. We chose to measure trait anxiety to examine beyond meal-related (state) anxiety.
Time frame: Baseline, 6 weeks, and 12 weeks
Population: All participants who completed a baseline study visit
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| PUFA | Beck Anxiety Inventory-Trait (BAIT) | Baseline | 26.4 Score on a scale | Standard Error 2.8 |
| PUFA | Beck Anxiety Inventory-Trait (BAIT) | 6 Weeks | 21.9 Score on a scale | Standard Error 2.8 |
| PUFA | Beck Anxiety Inventory-Trait (BAIT) | 12 Weeks | 14.9 Score on a scale | Standard Error 3 |
| Placebo | Beck Anxiety Inventory-Trait (BAIT) | Baseline | 19.3 Score on a scale | Standard Error 3 |
| Placebo | Beck Anxiety Inventory-Trait (BAIT) | 6 Weeks | 11 Score on a scale | Standard Error 3 |
| Placebo | Beck Anxiety Inventory-Trait (BAIT) | 12 Weeks | 6.5 Score on a scale | Standard Error 3.3 |
Other Pre-specified
Number of Participant Tolerating Saliva Collection and 24 Hour Heart Rate Monitor Use
At baseline, 6 weeks, and 12 weeks, study participants were asked to collect salivary samples 5 times over a 24 hour period. In addition, participants were asked to wear a 24 hour heart monitor during this same 24 hour interval. Compliance wtth completion of these physiological measures was assessed as follows: 1. For saliva collection, compliance was assessed by return of 5 full vials of saliva with record of time collected. 2. For 24 hour heart rate monitor, compliance was assessed by return of monitor with then downloading of data to confirm that the participant wore the device during the specified time interval.
Time frame: Baseline, 6 weeks, and 12 weeks
Population: All participants completing at least a baseline visit.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| PUFA | Number of Participant Tolerating Saliva Collection and 24 Hour Heart Rate Monitor Use | Tolerated Saliva Collection | 12 Participants |
| PUFA | Number of Participant Tolerating Saliva Collection and 24 Hour Heart Rate Monitor Use | Tolerated 24 Hour Heart Rate Monitor | 12 Participants |
| Placebo | Number of Participant Tolerating Saliva Collection and 24 Hour Heart Rate Monitor Use | Tolerated Saliva Collection | 12 Participants |
| Placebo | Number of Participant Tolerating Saliva Collection and 24 Hour Heart Rate Monitor Use | Tolerated 24 Hour Heart Rate Monitor | 12 Participants |