Clinical trial NCT05745194: Influence of Nutrition in Depression Treatment (INDEPT)
Official title: Nutritional Counselling Promoting Adherence to the Mediterranean Diet as Adjuvant in the Treatment of Major Depressive Disorder: A Randomized Open Controlled Trial Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Major Depressive Disorder - MDD
Keywords: Depression
Major Depressive Disorder
Nutritional Intervention
Randomized Controlled Trial
Mediterranean Diet
Lead sponsor: Associacao para Investigacao e Desenvolvimento da Faculdade de Medicina - CETERA
Sponsor class: OTHER
Collaborators: name: University of Lisbon
name: Instituto Politécnico de Leiria
name: Fundação para a Ciência e a Tecnologia
First posted: 2023-02-27
Enrollment: 190
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The study will follow a randomized open controlled trial design with concealment of participants allocation to the researchers involved in data collection at the end of the trial and follow-up assessments.

Researchers participating in the statistical analysis of the trial´s data will also be concealed to group allocation.

Participants meeting all inclusion criteria will be randomized to (a) the intervention group: six nutritional consultations with a registered nutritionist promoting adherence to the MedDiet and TAU or (b) the control group: only exposed to TAU for MDD.
Primary purpose: TREATMENT

Brief summary: The hypothesis to be tested by this study is that an intervention promoting adherence to the MedDiet can decrease symptoms of depression in patients with elevated inflammation biomarkers, namely C-reactive protein (CRP) and Interleukin 6 (IL-6) diagnosed with Major Depression Disorder (MDD), under treatment with antidepressant medication for a period of time less than or equal to 6 months.

The main aim of this study is to understand if promoting the adherence to the MedDiet, as an adjuvant strategy in the treatment of MDD, is effective in decreasing symptoms of depression in MDD patients, with elevated levels of inflammation biomarkers.

Other specific objectives of the study are

1. To assess the association between adherence to MedDiet and changes in inflammatory biomarkers;
2. To assess the association between changes in inflammatory biomarkers with symptoms of MDD;
3. To evaluate the association between adherence to MedDiet and effectiveness of psychiatric treatment of MDD;
4. To characterize the association between adherence to MedDiet and changes in health-related quality of life
5. To evaluate the economic cost-effectiveness of dietary counselling, as an adjuvant treatment in MDD.

The study will have a duration of 12 weeks, with a randomized parallel-group open controlled trial design, with two parallel groups with an allocation ratio of 1:1 - (a) intervention arm with six nutritional consultations with a registered nutritionist, promoting adherence to MedDiet, in addition to MDD Treatment-As-Usual (TAU) and (b) control group arm benefitting only from MDD TAU. A follow up assessment will be performed at 6- and 12-months.

Having into consideration an attrition of 40 percentage at the end of the intervention, the minimum sample size estimated is 190 (95 per arm).

The main outcome of the trial, changes in symptoms of depression, will be evaluated using the Beck Depression Inventory Second Edition (BDI-II).

Detailed description: To test the study´s hypothesis, namely if an intervention promoting adherence to the MedDiet can decrease symptoms of depression in patients with MDD and elevated inflammation biomarkers, the following objectives will be assessed.

The main objective of the trial is:

1.To assess the effectiveness of dietary counselling promoting MedDiet, as an adjuvant treatment of MDD, to decrease depressive symptoms in adults diagnosed with MDD and having elevated inflammation biomarkers (CRP, IL-6).

Specific objectives are:

1. To assess the association between adherence to MedDiet and changes in inflammatory biomarkers
2. To assess the association between changes in inflammatory biomarkers with symptoms of MDD
3. To evaluate the association between adherence to MedDiet and effectiveness of psychiatric treatment of MDD
4. Characterize the association between adherence to MedDiet and changes in health-related quality of life
5. To evaluate the economic cost-effectiveness of dietary counselling, as an adjuvant treatment in MDD

This study is a 12-week multicentre randomized parallel-group open controlled trial, with a follow up assessment at 6- and 12-months after baseline data collection, with two parallel groups with an allocation ratio of 1:1. - (a) intervention arm with six nutrition consultations with a registered nutritionist, promoting adherence to MedDiet, in addition to MDD treatment as usual (TAU) and (b) control group benefitting only from MDD TAU. Participants will be individuals diagnosed with a first episode of MDD, according to the "F32 Depressive episode" (F32.0; F32.1; F32.2) classification of the Tenth Revision of the International Classification of Diseases (ICD-10), under treatment with antidepressant medication for a period of time less than or equal to 6 months, attending to outpatient consultations.

Potential participants will be invited to enrol by their medical doctors from the participating recruitment centres. The invitation will be made at regular medical appointments including primary care consultations and outpatient psychiatric consultations in one of the participant centers. After signing the informed consent, CRP and IL-6 levels will be tested. Participants with increased inflammatory biomarkers, meeting all other inclusion criteria will be randomized to (a) the intervention arm or (b) the control arm of the study, in a 1:1 ratio, using a computer-generated list of random numbers stratified by center in variable blocks of size 2, 4 and 6. Treatment allocation will be concealed from the researchers, using sequentially numbered, opaque, sealed envelopes.

The study will use a convenience sample from patients diagnosed with MDD attending to outpatient consultations in one for the participating clinics.

Considering a 2-sided significance level of 5 percent and a power of 80 percent and having into consideration an attrition of 40 percent at the end of the intervention, the minimum sample size estimated is 190 (95 per arm). Estimating a prevalence of elevated inflammation in 30 percentage of MDD patients and 10 percentage of patients that don't meet other inclusion criteria, the number of recruited participants estimated is 700.

Participants allocated to the intervention group will attend six nutrition consultations, performed by a register nutritionist in weeks 1, 2, 4, 6, 8 and 10. The intervention will be personalized to each participant and will promote adherence to the Mediterranean Diet, ad libitum, without calories or macronutrients restriction or recommendation for weight change.

The intervention will follow a similar approach to the one proposed by Estruch et al. in the "Primary Prevention of Cardiovascular Disease with a Mediterranean Diet" study.

The intervention will contemplate the following recommendations:

Positive recommendations (promotion of the intake of the following foods):

1. Use of olive oil as main fat, both for cooking and dressing;
2. 2 or more servings of vegetables daily (200g of vegetables per serving);
3. 2-3 servings of fresh fruits per day;
4. 3 or more servings of legumes per day;
5. 3 or more servings of fish per week (100 - 150g of fish per serving or 200g of shellfish);
6. 3 or more servings of nuts a week (30g of nuts per serving);
7. Meat consumption mainly from poultry (without skin) or rabbit;
8. Home cooked meals with tomato, garlic and onion, at least twice a week;

Negative recommendations (eliminate or drastically reduce the following foods):

1. Cream, butter and margarine;
2. Cold meats, paté and duck meat;
3. Carbonated and/or sugared beverages;
4. Pastries and industrial baked products (cakes, donuts or cookies);
5. Industrial deserts;
6. French fries and potato chips;
7. Pre-cooked cakes and sweets;
8. If alcohol is consumed should be limited to 300ml of wine per day (150cc at meals for men and 100cc for woman, during meals);

Training of the nutritionists delivering the intervention will be provided prior to the beginning of recruitment and during the duration of the trial in MDD, therapeutic relationship, trauma and Mediterranean Diet.

Data analysis and reporting will be performed in accordance with Consolidated Standards of Reporting Trials (CONSORT) guidelines.

Primary analysis will include all randomized participants, following an intention-to-treat (ITT) approach. Baseline characteristics of the participants, by group, will be reported using descriptive statistics and compared by χ\^2 and t-test for independent samples (or equivalent non-parametric test).

To evaluate the effectiveness of nutritional counselling promoting MedDiet, the scale BDI-II will be used categorically in accordance with the standardized cutoffs: minimal depression (0-13), mild depression (14-19), moderate depression (20-28), severe depression (29-63). The success measure will be a decrease in category in the severity of depressive symptoms. The proportion of participants with a decrease in depression severity symptoms category according to the BDI-II (main outcome) will be compared between control and intervention groups using generalized linear mixed models.

Further adjustment for relevant covariates, as supportive analysis, will be made. Secondary analyses, including the analysis of the main outcome measure (BDI-II) as a continuous variable, will be conducted using (Generalized) Linear Mixed Models, as appropriate. For each outcome, results for either intervention and control group, and estimates of effect size with a 95 percent confidence interval will be reported. All analyses will be performed using R and R Studio version 3.5.3 and R Studio version 1.3.618 (or another updated version in the moment of analysis), assuming a significance level of 5 percent.

Eligibility criteria: Inclusion Criteria:

1. Aged between 18-70 years old
2. Able to understand and provide informed consent
3. Able to read and write
4. Have a diagnosis of MDD (according to ICD-10 F32.0; F32.1; F32.2; F32.9; F33.0; F33.1; F33.2; F33.9 criteria)
5. Score on the Beck Depression Inventory-II scale (BDI-II) \> 13;
6. Elevated biomarkers of inflammation (CRP \> 3mg/l or IL-6 ≥ 2pg/ml )
7. Able to follow a MedDiet without impeditive physical or religious limitations, allergies or intolerances
8. Being under pharmacological treatment for depressive disorder

Exclusion Criteria:

1. Diagnosis of autoimmune diseases, thyroid dysfunction or cancer
2. Diagnosis of bipolar disorder, psychotic disorders, eating disorders
3. Self-reported acute infection 2 weeks prior to the blood sample collection
4. Pregnancy or lactation
5. Glucocorticoid medication
6. Prescribed with NMDA Receptor Antagonists
7. Under treatment with brain stimulation techniques for the depressive episode
8. Currently participating in another intervention targeting diet, physical exercise, or MDD treatment

Primary outcomes:
measure: Changes in symptoms of MDD
timeFrame: Baseline, 12-weeks, 6-months, and 12-months after the baseline assessment
Secondary outcomes:
measure: Inflammation biomarkers (IL-6 and/or CRP)
timeFrame: Baseline, 12-weeks, 6-months, and 12-months after the baseline assessment
Other outcomes:
measure: Adherence to the Mediterranean Diet according to the 14-point Mediterranean Diet Adherence Screener Scale
timeFrame: Baseline,12-weeks, 6-months, and 12-months after the baseline assessment
measure: Health-related quality of life
timeFrame: Baseline, 12-week, 6-months, and 12-months after the baseline assessment
measure: Healthcare use cost
timeFrame: Baseline,12-weeks, 6-months, and 12-months after the baseline assessment
measure: Absenteeism
timeFrame: Baseline,12-weeks, 6-months, and 12-months after the baseline assessment
Locations:
city: Loures
country: Portugal
facility: Hospital de Beatriz Ângelo - Hospital de Loures, EPE
state: Lisboa
city: Leiria
country: Portugal
facility: Centro Hospitalar de Leiria - Hospital Santo André
Study officials:
affiliation: Instituto de Saúde Ambiental, Faculdade de Medicina da Universidade de Lisboa, Portugal
name: Maria João Heitor, PhD
role: PRINCIPAL_INVESTIGATOR
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