- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05558995
Ketogenic Diet Therapy Major Depressive Disorder (KETOMDD)
Effects and Mechanistic Aspects of Ketogenic Diet in Individuals With Major Depressive Disorder: A Pilot Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Elisa Brietzke, MD,Ph.D
- Phone Number: +1 (613) 548- 3232
- Email: Elisa.brietzke@queensu.ca
Study Contact Backup
- Name: Fabiano Gomes, MD, PhD
- Email: fabiano.alvesgomes@queensu.ca
Study Locations
-
-
Ontario
-
Kingston, Ontario, Canada, K7L 2V7
- Recruiting
- Queen's University - Kingston General Hospital
-
Contact:
- Elisa Brietzke, MD, PhD
- Phone Number: +1(613)548-3232
- Email: keto@queensu.ca
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
Diagnostic criteria for single episode or recurrent MDD, without psychotic features, according to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), and confirmed by the Mini International Neuropsychiatric Interview (MINI).
-- Moderate or severe depressive syndrome, as defined by a Montgomery-Asberg Depression Rating Scale (MADRS) total score greater than or equal to (>=) 20 at baseline.
- Treatment with SSRIs for at least 6 weeks, with no changes in dosing for the past 3 weeks.
- Must be capable of providing informed consent, based on the opinion of the participating physician.
- No vitamin and mineral deficiencies, specifically: vitamin B (B1, B3, B6, B9, and B12), vitamin D, iron, zinc, electrolytes (Na, K), calcium, and magnesium.
Exclusion Criteria:
- Has a current or prior diagnosis of schizophrenia spectrum disorders or bipolar disorder or related disorders, or intellectual disability, according to DSM-5.
- Has current or prior diagnosis of epilepsy
- Has homicidal ideation/intent or is at imminent risk of suicide per the physician's clinical judgment and/or based on the Columbia-Suicide Severity Rating Scale (C-SSRS) corresponding to a response of "Yes" on Item 4 (active suicidal ideation with some intent to act, without specific plan) or Item 5 (active suicidal ideation with specific plan and intent)
- Has received electroconvulsive therapy in the past 6 months. - Made use of caloric restriction, intermittent fasting, and carbohydrates restriction in the 4 weeks prior the inclusion.
- Adoption of specific dietetic habits: vegan, gluten-free, lactose-free diets or currently doing fasting for religious purposes.
- Has evidence of alcohol or drug dependence (except for nicotine and caffeine) according to DSM-5 or within 6 months prior to enrolment
- Has participated in or is currently enrolled in any clinical trial or observational study within the current episode.
- Has a medical contra-indication for ketogenic diet (e.g. metabolic disorder, cardiac arrhythmia, pregnancy or breastfeeding).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: MDD patient
Male and female participants (N=10) with ages between 18 and 50 have a confirmed diagnosis of major depressive episode, are experiencing a current episode (following DSM-5 criteria),
|
All the subjects will be instructed by a nutrition professional to have at least 3 meals per day consisting of 20 g to 30 g of carbohydrate in the form of green vegetables and salad, and 80 g to 100 g of protein in the form of meat, fish, fowl, eggs, shellfish and cheese for 12 weeks.
Polyunsaturated and monounsaturated fats will also be included in the diet.
Micronutrients (vitamins and minerals) will be given to each subject in the form of one capsule per day.
The adherence to diet will be confirmed weekly through a food log and urinary ketones assessment using dipstick to ensure that all individuals remain in a ketotic state.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Participant Adherence
Time Frame: Baseline (week 0), week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11, week 12.
|
Number of participants that completed the trial/Total number of participants enrolled
|
Baseline (week 0), week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11, week 12.
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in depressive symptoms severity
Time Frame: Baseline (week 0), week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11, week 12.
|
Montgomery-Asberg Depression Rating Scale to assess changes in severity of depressive symptoms.
The scores of this scale varies from 0-60 with higher scores indicating more severe depressive symptoms.
|
Baseline (week 0), week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11, week 12.
|
Changes in anxiety symptoms severity
Time Frame: Baseline (week 0), week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11, week 12.
|
Generalized Anxiety Disorder-7 to assess severity of anxiety symptoms.
The scores in this instrument vary from 0-21 with higher scores indication greater severity of anxiety symptoms.
|
Baseline (week 0), week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11, week 12.
|
Changes in functioning
Time Frame: Baseline (week 0), week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11, week 12.
|
Clinical Global Impression.
The score of this scale varies from 1-7, with higher scores indicating poorer functioning
|
Baseline (week 0), week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11, week 12.
|
complete blood count (CBC) baseline
Time Frame: Baseline (week 0)
|
complete blood count (CBC) as part of safety assessment
|
Baseline (week 0)
|
complete blood count (CBC) endopoint
Time Frame: Endpoint (week 12)
|
complete blood count (CBC) as part of the safety assessment
|
Endpoint (week 12)
|
Sodium blood level baseline
Time Frame: Baseline (week 0)
|
Sodium blood level blood expressed in mEq/L as part of the safety assessment
|
Baseline (week 0)
|
Sodium blood level endpoint
Time Frame: Endpoint (week 12)
|
Sodium blood level blood expressed in mEq/L as part of the safety assessment
|
Endpoint (week 12)
|
Potassium blood level baseline
Time Frame: Baseline (week 0)
|
Potassium blood level blood expressed in mEq/L as part of the safety assessment
|
Baseline (week 0)
|
Potassium blood level endpoint
Time Frame: Endpoint (week 12)
|
Potassium blood level blood expressed in mEq/L as part of the safety assessment
|
Endpoint (week 12)
|
Vitamin B blood level baseline
Time Frame: Baseline (week 0)
|
Vitamin B blood level expressed in pg/mL as part of the safety assessment
|
Baseline (week 0)
|
Vitamin B blood level endpoint
Time Frame: Endpoint (week 12)
|
Vitamin B blood level expressed in pg/mL as part of the safety assessment
|
Endpoint (week 12)
|
Vitamin D blood level baseline
Time Frame: Baseline (week 0)
|
Vitamin D blood level expressed in pg/mL as part of the safety assessment
|
Baseline (week 0)
|
Vitamin D blood level
Time Frame: Endpoint (week 12)
|
Vitamin D blood level expressed in pg/mL as part of the safety assessment
|
Endpoint (week 12)
|
Iron serum level baseline
Time Frame: Baseline (week 0)
|
Iron serum level expressed in mcg/dL as part of the safety assessment
|
Baseline (week 0)
|
Iron serum level endpoint
Time Frame: Endpoint (week 12)
|
Iron serum level expressed in mcg/dL as part of the safety assessment
|
Endpoint (week 12)
|
Zinc blood level baseline
Time Frame: Baseline (week 0)
|
Zinc blood level expressed in mcg/mL as part of the safety assessment
|
Baseline (week 0)
|
Zinc blood level endpoint
Time Frame: Endpoint (week 12)
|
Zinc blood level expressed in mcg/mL as part of the safety assessment
|
Endpoint (week 12)
|
Blood level of aspartate aminotransferase (AST) baseline
Time Frame: Baseline (week 0)
|
Blood level of aspartate aminotransferase (AST) expressed in U/L
|
Baseline (week 0)
|
Blood level of aspartate aminotransferase (AST) endpoint
Time Frame: Endpoint (week 12)
|
Blood level of aspartate aminotransferase (AST) expressed in U/L as part of the safety assessment
|
Endpoint (week 12)
|
Blood level of alanine aminotransferase (ALP) baseline
Time Frame: Baseline (week 0)
|
Blood level of alanine aminotransferase (ALP) expressed in U/L as part of the safety assessment
|
Baseline (week 0)
|
Blood level of alanine aminotransferase (ALP) endpoint
Time Frame: Endpoint (week 12)
|
Blood level of alanine aminotransferase (ALP) expressed in U/L as part of the safety assessment
|
Endpoint (week 12)
|
Blood level of albumin baseline
Time Frame: Baseline (week 0)
|
Blood level of albumin (ALB) expressed in g/dL as part of the safety assessment
|
Baseline (week 0)
|
Blood level of albumin endpoint
Time Frame: Endpoint (week 12)
|
Blood level of albumin (ALB) expressed in g/dL as part of the safety assessment
|
Endpoint (week 12)
|
Blood prothrombin time (PT) baseline
Time Frame: Baseline (week 0)
|
Prothrombin time (PT) expressed in prothrombin time/international normalized ratio (INR) as part of the safety assessment
|
Baseline (week 0)
|
Blood prothrombin time (PT) endpoint
Time Frame: Endpoint (week 12)
|
Prothrombin time (PT) expressed in prothrombin time/international normalized ratio (INR) as part of the safety assessment
|
Endpoint (week 12)
|
Total serum bilirubin baseline
Time Frame: Baseline (week 0)
|
Total serum bilirubin expressed in mg/dL as part of the safety assessment
|
Baseline (week 0)
|
Total serum bilirubin endpoint
Time Frame: Endpoint (week 12)
|
Total serum bilirubin expressed in mg/dL as part of the safety assessment
|
Endpoint (week 12)
|
Serum blood urea nitrogen (BUN) baseline
Time Frame: Baseline (week 0)
|
blood urea nitrogen (BUN) expressed in mmol/L as part of the safety assessment
|
Baseline (week 0)
|
blood urea nitrogen (BUN) endpoint
Time Frame: Endpoint (week 12)
|
blood urea nitrogen (BUN) expressed in mmol/L as part of the safety assessment
|
Endpoint (week 12)
|
Urinalysis (UA) baseline
Time Frame: Baseline (week 0)
|
Urinalysis (UA) for ketonuria as part of the safety assessment
|
Baseline (week 0)
|
Urinalysis (UA) endpoint
Time Frame: Endpoint (week 12)
|
Urinalysis (UA) for ketonuria as part of the safety assessment
|
Endpoint (week 12)
|
Blood glycated hemoglobin (HbA1c) in the baseline
Time Frame: Baseline (week 12)
|
Blood glycated hemoglobin (HbA1c), expressed in % as port of the safety assessment
|
Baseline (week 12)
|
Blood glycated hemoglobin (HbA1c) in the endpoint
Time Frame: Endpoint (week 12)
|
Blood glycated hemoglobin (HbA1c), expressed in % as part of the safety assessment
|
Endpoint (week 12)
|
Lipid panel baseline
Time Frame: Baseline (week 0)
|
lipid panel as part of the safety assessment
|
Baseline (week 0)
|
Lipid panel endpoint
Time Frame: Endpoint (week 12)
|
lipid panel as part of the safety assessment
|
Endpoint (week 12)
|
Pregnancy test (for female participants)
Time Frame: Baseline (week 0)
|
Pregnancy test (for female participants)
|
Baseline (week 0)
|
Pregnancy test (for female participants)
Time Frame: Endpoint (week 12)
|
Pregnancy test (for female participants)
|
Endpoint (week 12)
|
Changes in severity of anhedonia
Time Frame: Baseline (week 0), week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11, week 12.
|
Snaith-Hamilton Pleasure Scale (SHAPS) to assess severity of anhedonia.
The scores varies from 0-14.
A higher total score indicates higher levels of anhedonia.
|
Baseline (week 0), week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11, week 12.
|
Changes in the Effort-based decision making
Time Frame: Baseline (week 0), week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11, week 12.
|
the Effort-Expenditure for Rewards Task (EEfRT or "effort"), a novel behavioral paradigm as a means of exploring effort-based decision-making in humans.
The proportion of hard-task choices indicates a more active reward system.
|
Baseline (week 0), week 1, week 2, week 3, week 4, week 5, week 6, week 7, week 8, week 9, week 10, week 11, week 12.
|
Changes in the serum levels of the brain-derived neurotrophic factor
Time Frame: Baseline (week 0) and week 12.
|
The BDNF levels will be determined in plasma with the enzyme-linked immunosorbent assay (ELISA), as part of the biomarkers assessments.
Results are expressed in pg/mL.
|
Baseline (week 0) and week 12.
|
Changes in the serum level of TNF-alpha
Time Frame: Baseline (week 0) and week 12.
|
The TNF-alpha blood levels will be determined by ultrasensitive ELISA.
The results will be expressed in pg/mL.
|
Baseline (week 0) and week 12.
|
Changes in the serum level of Interleukin-1(IL-1)
Time Frame: Baseline (week 0) and week 12.
|
The IL-1 blood levels will be determined by ultrasensitive ELISA.
The results will be expressed in pg/mL.
|
Baseline (week 0) and week 12.
|
Changes in the serum level of Interleukin-6 (IL-6)
Time Frame: Baseline (week 0) and week 12.
|
The IL-6 blood levels will be determined by ultrasensitive ELISA.
The results will be expressed in pg/mL.
|
Baseline (week 0) and week 12.
|
Changes in the serum level of Interleukin-6 (IL-10)
Time Frame: Baseline (week 0) and week 12.
|
The IL-10 blood levels will be determined by ultrasensitive ELISA.
The results will be expressed in pg/mL.
|
Baseline (week 0) and week 12.
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Elisa Brietzke, MD,PhD, Queen's University
Publications and helpful links
General Publications
- Malhi GS, Mann JJ. Depression. Lancet. 2018 Nov 24;392(10161):2299-2312. doi: 10.1016/S0140-6736(18)31948-2. Epub 2018 Nov 2.
- Shelton RC, Tomarken AJ. Can recovery from depression be achieved? Psychiatr Serv. 2001 Nov;52(11):1469-78. doi: 10.1176/appi.ps.52.11.1469.
- Cooper JA, Arulpragasam AR, Treadway MT. Anhedonia in depression: biological mechanisms and computational models. Curr Opin Behav Sci. 2018 Aug;22:128-135. doi: 10.1016/j.cobeha.2018.01.024.
- Ceolin G, Breda V, Koning E, Meyyappan AC, Gomes FA, Moreira JD, Gerchman F, Brietzke E. A Possible Antidepressive Effect of Dietary Interventions: Emergent Findings and Research Challenges. Curr Treat Options Psychiatry. 2022;9(3):151-162. doi: 10.1007/s40501-022-00259-1. Epub 2022 Apr 23.
- Grigolon RB, Gerchman F, Schoffel AC, Hawken ER, Gill H, Vazquez GH, Mansur RB, McIntyre RS, Brietzke E. Mental, emotional, and behavioral effects of ketogenic diet for non-epileptic neuropsychiatric conditions. Prog Neuropsychopharmacol Biol Psychiatry. 2020 Aug 30;102:109947. doi: 10.1016/j.pnpbp.2020.109947. Epub 2020 Apr 17.
- Brietzke E, Mansur RB, Subramaniapillai M, Balanza-Martinez V, Vinberg M, Gonzalez-Pinto A, Rosenblat JD, Ho R, McIntyre RS. Ketogenic diet as a metabolic therapy for mood disorders: Evidence and developments. Neurosci Biobehav Rev. 2018 Nov;94:11-16. doi: 10.1016/j.neubiorev.2018.07.020. Epub 2018 Jul 31.
Study record dates
Study Major Dates
Study Start (Estimated)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Estimated)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- KETOOPEN
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Major Depressive Disorder
-
Shalvata Mental Health CenterUnknownMAjor Depressive DisorderIsrael
-
York UniversityCentre for Addiction and Mental HealthSuspendedDisorder, Major DepressiveCanada
-
Seasons Biotechnology (Taizhou) Co., Ltd.CompletedMajor Depressive Disorder (MDDIndia
-
Gangnam Severance HospitalCompletedMajor Depressive Disorder(MDD)Korea, Republic of
-
University College, LondonCompletedUnipolar Major Depressive DisorderUnited Kingdom
-
Fundació Institut de Recerca de l'Hospital de la...Fondo de Investigacion SanitariaUnknown
-
Seasons Biotechnology (Taizhou) Co., Ltd.CompletedMajor Depressive Disorder (MDD)India
-
Repurposed Therapeutics, Inc.Unknown
-
GlaxoSmithKlineCompletedMajor Depressive Disorder (MDD)United States
-
AccexibleRecruitingMajor Depressive Disorder (MDD)Spain
Clinical Trials on ketogenic diet
-
Shriners Hospitals for ChildrenUniversity of HawaiiCompleted
-
University of PittsburghBaszucki Brain Research FundRecruitingBipolar DisorderUnited States
-
University of Roma La SapienzaCompleted
-
Kuopio University HospitalDeakin UniversityRecruitingPsychotic Disorders | Schizophrenia | Psychosis | Psychosis; AcuteFinland
-
Mid-Atlantic Epilepsy and Sleep Center, LLCUnknown
-
University of FloridaRecruitingSeizuresUnited States
-
Helse Nord-Trøndelag HFNorwegian University of Science and Technology; Vanderbilt University Medical... and other collaboratorsActive, not recruiting
-
Chang Gung Memorial HospitalRecruitingSystemic Lupus Erythematosus | Ketogenic DietingTaiwan
-
Attikon HospitalActive, not recruitingObesity and PsoriasisGreece
-
University of Roma La SapienzaCompleted