Clinical trial NCT04398784: Effect of Whole Blueberry Powder Consumption on Depression in a Central Louisiana Population
Official title: Effect of Whole Blueberry Powder Consumption on Depression: A Randomized, Double-blind, Placebo Controlled, Crossover Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Depression
Depression, Anxiety
Inflammation
Keywords: depression
inflammation
anxiety
blueberries
Lead sponsor: Louisiana State University, Baton Rouge
Sponsor class: OTHER
Collaborators: name: U.S. Highbush Blueberry Council
name: Louisiana Health Care Practitioners, LLC
name: Collective Healthcare Solutions, LLC
name: uBiome, Inc.
First posted: 2020-05-21
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This study will utilize a randomized, double-blind, placebo-controlled, crossover design. 60 participants with depression will be randomized into either the placebo first or blueberry first group. Randomization will be based on outcomes from behavioral measures (Major Depression Inventory and GAD-7) and a physiological measure (C-reactive protein levels) in appointment 0. The first arm will consist of 12 weeks of daily treatment and baseline (pre-intervention), mid-intervention and post-intervention assessments. Next there will be a four week washout period, after which patients will switch treatments, and the second arm will commence--identical to the first in structure. Further, the study is a repeated measures design with each participant's baseline measures serving as her or his own control.
Primary purpose: TREATMENT

Brief summary: This pilot study aims to measure the effects of an intervention of 22.5 grams of freeze-dried whole blueberry powder in water drunk daily. Measures are on outcomes of depression, biological markers of inflammation and oxidative stress, and microbial populations in the intestines.

Detailed description: A 29 week double-blind, placebo-controlled, crossover intervention assessing the effect of a blueberries on behavioral symptoms related to depression, biological markers of inflammation and oxidative stress, and gut microbiome measures. A total of 45 participants will be randomly assigned to either a blueberry-first or placebo-first group; participants will take 22.5 grams of either freeze-dried blueberry powder or matched placebo powder mixed with water daily for 12 weeks. This period is followed by a 4 week washout period at the beginning of which all participants will stop the assigned intervention. After this washout the participants will start their crossover intervention.

Eligibility criteria: Inclusion Criteria:

* Participants with a stable diagnosis of Major Depressive Disorder (\>1 year prior to enrollment)
* Males and females 18-70 years of age
* Subjects with sleep disruptions
* Subjects currently prescribed to a non-antipsychotic mono-pharmacotherapies
* English speaking subjects only (all evaluations are in English)

Subjects with the following inflammatory disorders that exhibit low to moderate symptoms:

* Hypertension (mild=140/80-160/90; moderate= 160/90-180/100)
* Asthma (requiring 2 or fewer inhalations of rescue inhaler per day)
* Gastroesophageal reflux disease
* Irritable bowel syndrome (controlled, \<3 bowel movements a day)
* Arthritis (controlled)
* Chronic stomach ulcers (controlled)
* Obesity BMI \<40
* Chronic pain
* Fibromyalgia
* Chronic Fatigue Syndrome
* Type I or Type II diabetes (controlled)
* Subjects that are compliant with current treatment regimens and clinic appointments
* Subjects taking intermittent or infrequent doses of acetaminophen or NSAIDs
* Subjects who currently smoke or have a history of smoking

Exclusion Criteria:

Subjects with current diagnosis or history of the following conditions; or subjects currently on medication for any of the following conditions:

* Severe Cardiovascular disease; Heart attack/pacemaker
* Cancer
* Autoimmunity Disorders
* Crohn's Disease or Ulcerative Colitis
* Alzheimer's Disease
* Parkinson's Disease
* Multiple Sclerosis
* Uncontrolled Diabetes: Type I or II
* Severe irritable bowel disease (\>3 stools per day)
* Hypertension (severe \>180/100)
* Hypotension (\<100/60)
* Epilepsy
* Autism Spectrum Disorder
* Schizophrenia
* Psychosis/Psychotic Symptoms
* Uncontrolled Hypo/Hyperthyroidism
* Women who are pregnant, nursing, lactating, or planning to become pregnant within timeline of study
* Subjects who are blind or deaf
* Subjects who are allergic to blueberries or other similar foods or drinks (e.g. wine), or subjects who are allergic to red or blue food dye agents
* Subjects who do not like the taste of blueberries
* Subjects who do not want to disclose information related to their Major Depressive Disorder
* Subjects who do not want to be subjected to blood draws
* Subjects who consume \>4 cups of blueberries per week or other foods/drinks with significant polyphenol content
* Subjects supplementing with elderberry syrup \>4 times per week
* Subjects who have a planned surgery during the timeline of the study
* Subjects prescribed to antipsychotics
* Subjects using acetaminophen or NSAIDS (drugs targeting pro-inflammatory paths) chronically or exceeding recommended daily doses
* Subjects chronically on Decadron, Dexamethasone, or Prednisone; or other oral steroids
* Subjects on any augmenting agents (the following is not an inclusive list):

Abilify (aripiprazole), Risperdal (risperidone), Zyprexa (olanzapine), Seroquel (quetiapine), Clozaril(clozapine), Symbyax (olanzapine/fluoxetine), Geodon (ziprasidone)

* Subjects supplementing with devil's claw, fenugreek, guar gum, Panax ginseng, and Siberian ginseng
* Subjects who have a history of suicidal ideation or suicide attempt
* Subjects with a history or record of physical violence toward self or others
* Subjects who will jeopardize their job if they miss work for appointments
* Subjects with a history of addiction, except cigarettes

Primary outcomes:
measure: Major Depression Inventory (MDI)
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Major Depression Inventory (MDI)
timeFrame: Day 30 of treatment intervention
measure: Major Depression Inventory (MDI)
timeFrame: Day 60 of treatment intervention
measure: Major Depression Inventory (MDI)
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Major Depression Inventory (MDI)
timeFrame: Day 30 of placebo intervention
measure: Major Depression Inventory (MDI)
timeFrame: Day 60 of placebo intervention
measure: Generalized Anxiety Disorder 7-item (GAD-7) scale
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Generalized Anxiety Disorder 7-item (GAD-7) scale
timeFrame: Day 30 of treatment intervention
measure: Generalized Anxiety Disorder 7-item (GAD-7) scale
timeFrame: Day 60 of treatment intervention
measure: Generalized Anxiety Disorder 7-item (GAD-7) scale
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Generalized Anxiety Disorder 7-item (GAD-7) scale
timeFrame: Day 30 of placebo intervention
measure: Generalized Anxiety Disorder 7-item (GAD-7) scale
timeFrame: Day 60 of placebo intervention
measure: Structured Interview Guide for the Hamilton Depression Scale and Inventory of Depressive Symptomatology-Clinician Rated (SIGHD-IDSC)
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Structured Interview Guide for the Hamilton Depression Scale and Inventory of Depressive Symptomatology-Clinician Rated (SIGHD-IDSC)
timeFrame: Day 60 of treatment intervention
measure: Structured Interview Guide for the Hamilton Depression Scale and Inventory of Depressive Symptomatology-Clinician Rated (SIGHD-IDSC)
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Structured Interview Guide for the Hamilton Depression Scale and Inventory of Depressive Symptomatology-Clinician Rated (SIGHD-IDSC)
timeFrame: Day 60 of placebo intervention
Secondary outcomes:
measure: C-Reactive Protein (CRP) Measure
timeFrame: Immediately after enrollment, 30 days before start of intervention
measure: CRP Measure
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: CRP Measure
timeFrame: Day 30 of treatment intervention
measure: CRP Measure
timeFrame: Day 60 of treatment intervention
measure: CRP Measure
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: CRP Measure
timeFrame: Day 30 of placebo intervention
measure: CRP Measure
timeFrame: Day 60 of placebo intervention
measure: Gut Microbiome Analysis
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Gut Microbiome Analysis
timeFrame: Day 30 of treatment intervention
measure: Gut Microbiome Analysis
timeFrame: Day 60 of treatment intervention
measure: Gut Microbiome Analysis
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Gut Microbiome Analysis
timeFrame: Day 30 of placebo intervention
measure: Gut Microbiome Analysis
timeFrame: Day 60 of placebo intervention
measure: Leeds Sleep Evaluation Questionnaire (LSEQ)
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Leeds Sleep Evaluation Questionnaire (LSEQ)
timeFrame: Day 30 of treatment intervention
measure: Leeds Sleep Evaluation Questionnaire (LSEQ)
timeFrame: Day 60 of treatment intervention
measure: Leeds Sleep Evaluation Questionnaire (LSEQ)
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Leeds Sleep Evaluation Questionnaire (LSEQ)
timeFrame: Day 30 of placebo intervention
measure: Leeds Sleep Evaluation Questionnaire (LSEQ)
timeFrame: Day 60 of placebo intervention
measure: Concentration of reactive oxygen species (ROS)
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Concentration of reactive oxygen species (ROS)
timeFrame: Day 30 of treatment intervention
measure: Concentration of reactive oxygen species (ROS)
timeFrame: Day 60 of treatment intervention
measure: Concentration of reactive oxygen species (ROS)
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Concentration of reactive oxygen species (ROS)
timeFrame: Day 30 of placebo intervention
measure: Concentration of reactive oxygen species (ROS)
timeFrame: Day 60 of placebo intervention
measure: Concentration of quinolinic acid
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Concentration of quinolinic acid
timeFrame: Day 30 of treatment intervention
measure: Concentration of quinolinic acid
timeFrame: Day 60 of treatment intervention
measure: Concentration of quinolinic acid
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Concentration of quinolinic acid
timeFrame: Day 30 of placebo intervention
measure: Concentration of quinolinic acid
timeFrame: Day 60 of placebo intervention
measure: Concentration of kynurenic acid
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Concentration of kynurenic acid
timeFrame: Day 30 of treatment intervention
measure: Concentration of kynurenic acid
timeFrame: Day 60 of treatment intervention
measure: Concentration of kynurenic acid
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Concentration of kynurenic acid
timeFrame: Day 30 of placebo intervention
measure: Concentration of kynurenic acid
timeFrame: Day 60 of placebo intervention
measure: Concentration of kynurenine
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Concentration of kynurenine
timeFrame: Day 30 of treatment intervention
measure: Concentration of kynurenine
timeFrame: Day 60 of treatment intervention
measure: Concentration of kynurenine
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Concentration of kynurenine
timeFrame: Day 30 of placebo intervention
measure: Concentration of kynurenine
timeFrame: Day 60 of placebo intervention
measure: Concentration of tryptophan
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Concentration of tryptophan
timeFrame: Day 30 of treatment intervention
measure: Concentration of tryptophan
timeFrame: Day 60 of treatment intervention
measure: Concentration of tryptophan
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Concentration of tryptophan
timeFrame: Day 30 of placebo intervention
measure: Concentration of tryptophan
timeFrame: Day 60 of placebo intervention
measure: Concentration of indoleamine 2,3-dioxygenase (IDO)
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Concentration of indoleamine 2,3-dioxygenase (IDO)
timeFrame: Day 30 of treatment intervention
measure: Concentration of indoleamine 2,3-dioxygenase (IDO)
timeFrame: Day 60 of treatment intervention
measure: Concentration of indoleamine 2,3-dioxygenase (IDO)
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Concentration of indoleamine 2,3-dioxygenase (IDO)
timeFrame: Day 30 of placebo intervention
measure: Concentration of indoleamine 2,3-dioxygenase (IDO)
timeFrame: Day 60 of placebo intervention
measure: Concentration suicide-associated protein spindle and kinetochore-associated protein 2 (SKA-2)
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Concentration of suicide-associated protein SKA-2
timeFrame: Day 30 of treatment intervention
measure: Concentration of suicide-associated protein SKA-2
timeFrame: Day 60 of treatment intervention
measure: Concentration of suicide-associated protein SKA-2
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Concentration of suicide-associated protein SKA-2
timeFrame: Day 30 of placebo intervention
measure: Concentration of suicide-associated protein SKA-2
timeFrame: Day 60 of placebo intervention
measure: Concentration of suicide-associated protein spermidine/spermine N1-acetyltransferase 1 (SAT-1)
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Concentration of suicide-associated protein SAT-1
timeFrame: Day 30 of treatment intervention
measure: Concentration of suicide-associated protein SAT-1
timeFrame: Day 60 of treatment intervention
measure: Concentration of suicide-associated protein SAT-1
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Concentration of suicide-associated protein SAT-1
timeFrame: Day 30 of placebo intervention
measure: Concentration of suicide-associated protein SAT-1
timeFrame: Day 60 of placebo intervention
measure: Concentration of suicide-associated protein solute carrier family 4 member 4 (SLC4A4)
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Concentration of suicide-associated protein SLC4A4
timeFrame: Day 30 of treatment intervention
measure: Concentration of suicide-associated protein SLC4A4
timeFrame: Day 60 of treatment intervention
measure: Concentration of suicide-associated protein SLC4A4
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Concentration of suicide-associated protein SLC4A4
timeFrame: Day 30 of placebo intervention
measure: Concentration of suicide-associated protein SLC4A4
timeFrame: Day 60 of placebo intervention
measure: Concentration of brain-derived neurotropic factor (BDNF)
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Concentration of brain-derived neurotropic factor (BDNF)
timeFrame: Day 30 of treatment intervention
measure: Concentration of brain-derived neurotropic factor (BDNF)
timeFrame: Day 60 of treatment intervention
measure: Concentration of brain-derived neurotropic factor (BDNF)
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Concentration of brain-derived neurotropic factor (BDNF)
timeFrame: Day 30 of placebo intervention
measure: Concentration of brain-derived neurotropic factor (BDNF)
timeFrame: Day 60 of placebo intervention
measure: Concentration of glial cell line-derived neurotropic factor (GDNF)
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Concentration of glial cell line-derived neurotropic factor (GDNF)
timeFrame: Day 30 of treatment intervention
measure: Concentration of glial cell line-derived neurotropic factor (GDNF)
timeFrame: Day 60 of treatment intervention
measure: Concentration of glial cell line-derived neurotropic factor (GDNF)
timeFrame: Day 1 of placebo intervention, before placebo intervention
measure: Concentration of glial cell line-derived neurotropic factor (GDNF)
timeFrame: Day 30 of placebo intervention
measure: Concentration of glial cell line-derived neurotropic factor (GDNF)
timeFrame: Day 60 of placebo intervention
measure: Concentration of serotonin related compound serotonin transporter (SERT)
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Concentration of serotonin related compound SERT
timeFrame: Day 30 of treatment intervention
measure: Concentration of serotonin related compound SERT
timeFrame: Day 60 of treatment intervention
measure: Concentration of serotonin related compound SERT
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Concentration of serotonin related compound SERT
timeFrame: Day 30 of placebo intervention
measure: Concentration of serotonin related compound SERT
timeFrame: Day 60 of placebo intervention
measure: Concentration of serotonin related compound 5-hydroxyindoleacetic acid (5-HIAA)
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Concentration of serotonin related compound 5-HIAA
timeFrame: Day 30 of treatment intervention
measure: Concentration of serotonin related compound 5-HIAA
timeFrame: Day 60 of treatment intervention
measure: Concentration of serotonin related compound 5-HIAA
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Concentration of serotonin related compound 5-HIAA
timeFrame: Day 30 of placebo intervention
measure: Concentration of serotonin related compound 5-HIAA
timeFrame: Day 60 of placebo intervention
measure: Concentration of glutamate
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Concentration of glutamate
timeFrame: Day 30 of treatment intervention
measure: Concentration of glutamate
timeFrame: Day 60 of treatment intervention
measure: Concentration of glutamate
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Concentration of glutamate
timeFrame: Day 30 of placebo intervention
measure: Concentration of glutamate
timeFrame: Day 60 of placebo intervention
measure: Concentration of glutamine
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Concentration of glutamine
timeFrame: Day 30 of treatment intervention
measure: Concentration of glutamine
timeFrame: Day 60 of treatment intervention
measure: Concentration of glutamine
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Concentration of glutamine
timeFrame: Day 30 of placebo intervention
measure: Concentration of glutamine
timeFrame: Day 60 of placebo intervention
measure: Concentration of cortisol
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Concentration of cortisol
timeFrame: Day 30 of treatment intervention
measure: Concentration of cortisol
timeFrame: Day 60 of treatment intervention
measure: Concentration of cortisol
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Concentration of cortisol
timeFrame: Day 30 of placebo intervention
measure: Concentration of cortisol
timeFrame: Day 60 of placebo intervention
measure: Concentration of inflammation biomarker interleukin 6 (IL-6)
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Concentration of inflammation biomarker interleukin 6 (IL-6)
timeFrame: Day 30 of treatment intervention
measure: Concentration of inflammation biomarker interleukin 6 (IL-6)
timeFrame: Day 60 of treatment intervention
measure: Concentration of inflammation biomarker interleukin 6 (IL-6)
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Concentration of inflammation biomarker interleukin 6 (IL-6)
timeFrame: Day 30 of placebo intervention
measure: Concentration of inflammation biomarker interleukin 6 (IL-6)
timeFrame: Day 60 of placebo intervention
measure: Concentration of inflammation biomarker interleukin 1 beta (IL-1beta)
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Concentration of inflammation biomarker interleukin 1 beta (IL-1beta)
timeFrame: Day 30 of treatment intervention
measure: Concentration of inflammation biomarker interleukin 1 beta (IL-1beta)
timeFrame: Day 60 of treatment intervention
measure: Concentration of inflammation biomarker interleukin 1 beta (IL-1beta)
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Concentration of inflammation biomarker interleukin 1 beta (IL-1beta)
timeFrame: Day 30 of placebo intervention
measure: Concentration of inflammation biomarker interleukin 1 beta (IL-1beta)
timeFrame: Day 60 of placebo intervention
measure: Concentration of inflammation biomarker interferon gamma (IFN-gamma)
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Concentration of inflammation biomarker interferon gamma (IFN-gamma)
timeFrame: Day 30 of treatment intervention
measure: Concentration of inflammation biomarker interferon gamma (IFN-gamma)
timeFrame: Day 60 of treatment intervention
measure: Concentration of inflammation biomarker interferon gamma (IFN-gamma)
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Concentration of inflammation biomarker interferon gamma (IFN-gamma)
timeFrame: Day 30 of placebo intervention
measure: Concentration of inflammation biomarker interferon gamma (IFN-gamma)
timeFrame: Day 60 of placebo intervention
measure: Concentration of inflammation biomarker tumour necrosis factor alpha (TNF-alpha)
timeFrame: Day 1 of treatment intervention, before treatment consumption
measure: Concentration of inflammation biomarker tumour necrosis factor alpha (TNF-alpha)
timeFrame: Day 30 of treatment intervention
measure: Concentration of inflammation biomarker tumour necrosis factor alpha (TNF-alpha)
timeFrame: Day 60 of treatment intervention
measure: Concentration of inflammation biomarker tumour necrosis factor alpha (TNF-alpha)
timeFrame: Day 1 of placebo intervention, before placebo consumption
measure: Concentration of inflammation biomarker tumour necrosis factor alpha (TNF-alpha)
timeFrame: Day 30 of placebo intervention
measure: Concentration of inflammation biomarker tumour necrosis factor alpha (TNF-alpha)
timeFrame: Day 60 of placebo intervention
Other outcomes:
Locations:
city: Cottonport
country: United States
facility: Cottonport Family Clinic
state: Louisiana
city: Marksville
country: United States
facility: Marksville Family Clinic
state: Louisiana
Study officials:
affiliation: Louisiana State University, Baton Rouge
name: Joseph Francis, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: