Bipolar I DisorderNCT06221852
Ketogenic and Nutritional Interventions for First Episode Bipolar Disorder
A study testing Ketogenic diet and Dietary Guidelines for Americans in people with Bipolar I Disorder and Psychosis, run by Mclean Hospital at 1 site in United States.
Trial summary
This is a randomized, controlled clinical trial to assess the effects of the ketogenic diet in combination with treatment as usual on brain energy metabolism and psychiatric symptoms in individuals with first episode bipolar disorder and schizoaffective disorder. Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Bipolar I Disorder, Psychosis, Schizoaffective Disorder
- What is being tested?
- Ketogenic diet and Dietary Guidelines for Americans
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 50 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Mar 2024to 30 Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Between the ages of 18 and 45.
- Ability to adhere to study diets.
- Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnosis of bipolar I disorder or schizoaffective disorder with onset of illness in the last 7 years.
- Must have a stable psychiatric disorder with no change in psychiatric medications within the past 2 weeks of screening
- Must not be expected to require addition of any new psychiatric medications during the 12-week duration of the study.
Who cannot join
- Unable to sign informed consent
- Contraindication to magnetic resonance (MR) scan (including claustrophobia)
- Unstable medical illness (including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease)
- Current DSM-5 substance use disorder
- Currently pregnant, nursing, or of childbearing potential and not using a medically accepted means of contraception
- Have a body weight of over 350 lbs or a body mass index (BMI) <20
Show all 13Show fewer
- Score above 15 on the Young Mania Rating Scale (YMRS)
- History of significant head injury
- Current cancer diagnosis
- Current diagnosis of type 1 or type 2 Diabetes Mellitus
- History of gastric bypass surgery or any weight loss surgery
- Concomitant treatment with Propofol
- Familial hypercholesterolemia
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Virginie-Anne Chouinard, MD contact
United States1 site, 1 recruiting
- Recruiting
McLean Hospital
Belmont, Massachusetts, 02478
Kaitlin Shannon, B.A., kshannon6@mgb.org
Virginie-Anne Chouinard, MD
About this study
Official title: A Randomized Controlled Clinical Trial of Ketogenic and Nutritional Interventions for Brain Energy Metabolism and Psychiatric Symptoms in First Episode Bipolar Disorder.
This is a randomized, controlled clinical trial to assess the effects of the ketogenic diet in combination with treatment as usual on brain energy metabolism and psychiatric symptoms in individuals with first episode bipolar disorder and schizoaffective disorder.
Read the detailed description
Several lines of evidence show energy metabolism and redox dysregulation in bipolar disorder and psychotic disorders. Ketogenic interventions targeting energy metabolism are promising therapeutic approaches to improve mood and psychosis in bipolar disorder and other psychotic disorders. Early intervention is also critical to helping people achieve their goals for recovery after a first episode. Investigators aim to use multimodal imaging and metabolic measures to study the effects of a ketogenic diet intervention on energy metabolism and psychiatric symptoms in individuals with first episode bipolar disorder and schizoaffective disorder. This 12-week randomized controlled trial will assess the benefits of a ketogenic diet in combination with treatment as usual compared to a standard diet. Investigators will measure the effects of nutritional ketosis on brain redox and energy metabolism and other neurometabolic markers using magnetic resonance spectroscopy. Furthermore, investigators will measure the effects of the ketogenic diet on mood and psychotic symptoms and metabolic measures such as insulin resistance.
- Conditions
- Bipolar I Disorder, Psychosis, Schizoaffective Disorder
- Being tested
- Ketogenic diet, Dietary Guidelines for Americans
- Keywords
- First episode psychosis, Ketogenic Diet, Keto, Brain energy metabolism, Insulin resistance, Schizoaffective Disorder, Bipolar Disorder, Magnetic resonance spectroscopy (MRS), Redox, Creatine kinase
- Medical subject headings
- Psychotic Disorders, Insulin Resistance, Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketogenic dietOther
The ketogenic diet (KD) is a normo-caloric diet composed of high-fat, low carbohydrate, and adequate protein intake. The KD will consist of 3 meals a day plus snacks, targeting 75-80% fat, 13-18% protein, 7% carbohydrates.
Dietary Guidelines for AmericansOther
Dietary Guidelines for Americans diet is a normo-caloric diet consisting of 3 meals a day plus snacks, emphasizing nutrient dense foods to meet food group needs (85% of calories), and limits foods and beverages higher in added sugars and saturated fat (15% of calories).
| Study group | Role | What they receive |
|---|---|---|
| Ketogenic diet arm | Active comparator | Eligible participants assigned to the ketogenic diet arm will be asked to follow the ketogenic diet (KD) for 12 weeks in addition to any ongoing medications (e.g., mood stabilizers and/or second-generation antipsychotics). Participants will receive weekly and as needed diet counseling from a registered dietician. Participants will be asked to monitor and report their blood ketone levels each day via a finger-prick device provided by the study team. Participants have the ability to opt into an optional open label phase where they can continue on the ketogenic diet with the daily finger pricks for another 12 weeks after the 12-week main study. Receives: Other: Ketogenic diet |
| Dietary Guidelines for Americans arm | Active comparator | Eligible participants assigned to the Dietary Guidelines for Americans (DGA) arm will adhere to the Dietary Guidelines for Americans in addition to any ongoing medications (e.g., mood stabilizers and/or second-generation antipsychotics). Participants will receive weekly and as needed diet counseling from a registered dietician. Participants will be asked to monitor and report their blood ketone levels each day via a finger-prick device provided by the study team. Participants have the ability to opt into an optional open label phase where they can switch to the ketogenic diet with the daily finger pricks for 12 weeks after the 12-week main study. Receives: Other: Dietary Guidelines for Americans |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in brain redox nicotinamide adenine dinucleotide metabolites ratio (NAD+/NADH)
Change from baseline to week 12 in NAD+/NADH as measured by in vivo phosphorus magnetic resonance spectroscopy (31P-MRS).
Measured: 12 weeks
Change in brain creatine kinase forward reaction rate (kf)
Change from baseline to week 12 in creatine kinase forward reaction rate (kf) as measured by 31P magnetization transfer (MT) MRS.
Measured: 12 weeks
Change in insulin resistance
Change from baseline to week 12 of insulin resistance measured using the homeostatic model assessment of insulin resistance (HOMA-IR) using fasting blood glucose and insulin levels.
Measured: 12 weeks
Change in psychotic symptoms
Change from baseline to week 12 in Positive and Negative Syndrome Scale (PANSS) total score. Scores range from 30-210; a higher score indicates a higher level of psychotic symptoms.
Measured: 12 weeks
Change in depressive symptoms
Change from baseline to week 12 in Hamilton Rating Scale for Depression (HAM-D) total score. Scores range from 0-52; a higher score indicates a higher level of depression.
Measured: 12 weeks
Change in mania symptoms
Change from baseline to week 12 in Young Mania Rating Scale (YMRS) total score. Scores range from 0-60. A higher score indicates a more severe illness.
Measured: 12 weeks
Change in Clinical Global Impression (CGI) Scale
Change from baseline to week 12 in Clinical Global Impression (CGI) Scale. Scores range from 1-7; a higher score indicates higher severity of illness.
Measured: 12 weeks
Secondary outcomes (21)
Change in body weight
Change from baseline to week 12 in participant body weight in kilograms, as measured using a standing scale.
Measured: 12 weeks
Change in glycated hemoglobin (Hemoglobin A1c) level
Change from baseline to week 12 in fasting Hemoglobin A1c level.
Measured: 12 weeks
Change in triglyceride levels
Change from baseline to week 12 in fasting triglyceride levels.
Measured: 12 weeks
Change in low-density lipoprotein (LDL) levels
Change from baseline to week 12 in fasting LDL levels.
Measured: 12 weeks
Change in high-density lipoprotein (HDL) levels
Change from baseline to week 12 in fasting HDL levels.
Measured: 12 weeks
Change in high-sensitivity C-reactive protein (hs-CRP) levels
Change from baseline to week 12 in fasting hs-CRP levels.
Measured: 12 weeks
Change in brain gamma-aminobutyric acid (GABA) concentration
Change from baseline to week 12 in GABA concentration measured by proton magnetic resonance spectroscopy.
Measured: 12 weeks
Change in brain glutamate metabolite concentration
Change from baseline to week 12 in glutamate metabolite concentration measured by proton magnetic resonance spectroscopy.
Measured: 12 weeks
Change in brain glutathione (GSH)
Change from baseline to week 12 in brain GSH measured by proton magnetic resonance spectroscopy.
Measured: 12 weeks
Change in brain Phosphocreatine (PCr)
Changes from baseline to week 12 in PCr concentration as measured by in vivo 31P-MRS.
Measured: 12 weeks
Change in brain pH
Change from baseline to week 12 in pH as measured by in vivo 31P MRS.
Measured: 12 weeks
Change in brain inorganic phosphate concentration
Change from baseline to week 12 in inorganic phosphate (Pi) concentration as measured by in vivo 31P MRS.
Measured: 12 weeks
Change in adverse events
Change from baseline to week 12 from baseline to week 12 in adverse events.
Measured: 12 weeks
Change in anxiety symptoms
Change from baseline to week 12 from baseline to week 12 in Hamilton Anxiety Rating Scale (HAM-A) total score. Scores range from 0 - 56; a higher score indicates a higher level of anxiety.
Measured: 12 weeks
Change in stress symptoms
Change from baseline to week 12 in Depression Anxiety Stress Scales (DASS-42) Stress Subscale score. Scores range from 0-42; a higher score indicates a higher level of stress.
Measured: 12 weeks
Change in cognitive performance
Change from baseline to week 12 in Matrics Consensus Cognitive Battery (MCCB) Total Score. Scores range from 0.00% - 100.00%; a higher score indicates higher cognition.
Measured: 12 weeks
Change in Global Functioning Scale (GFS) - Social and Role total score
Change from baseline to week 12 in Global Functioning Scale (GFS) - Social and Role total score. Scores range from 6-60; a lower score indicates worse social and role functioning.
Measured: 12 weeks
Change in cell-free mitochondrial DNA (cf-mtDNA)
Change from baseline to week 12 in blood and saliva cf-mtDNA levels.
Measured: 12 weeks
Change in growth differentiation factor 15 (GDF15)
Change from baseline to week 12 in blood and saliva GDF15 levels.
Measured: 12 weeks
Change in blood NAD/NADH+ ratio
Change from baseline to week 12 in blood NAD/NADH+ ratio.
Measured: 12 weeks
Change in blood GSH/GSSH ratio
Change from baseline to week 12 in blood GSH/GSSH ratio.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jan 2024
- Study start12 Mar 2024
- Primary completion30 Sep 2027 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bipolar I DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mclean Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Baszucki Family Foundation
- Responsible party
- Principal investigator, Virginie-Anne Chouinard, MD, Mclean Hospital
- Investigators
- Virginie-Anne Chouinard, MD, Principal investigator, Mclean Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06221852
- Sponsor's protocol ID
- 2023P002849
- Status last verified
- Nov 2025
- First submitted
- 11 Jan 2024
- Last updated
- 17 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 17 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Clinical Trial of Ketogenic and Nutritional Interventions for Brain Energy Metabolism and Psychiatric Symptoms in First Episode Bipolar Disorder.
- ClinicalTrials.gov ID
- NCT06221852
- Acronym / sponsor ID
- 2023P002849
- Conditions
- Bipolar I Disorder, Psychosis, Schizoaffective Disorder
- Keywords
- First episode psychosis, Ketogenic Diet, Keto, Brain energy metabolism, Insulin resistance, Schizoaffective Disorder, Bipolar Disorder, Magnetic resonance spectroscopy (MRS)
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Mclean HospitalUniversity, hospital or other
- Collaborators
- Baszucki Family Foundation
- Study start
- 12 Mar 2024 (actual)
- Primary completion
- 30 Sep 2027 (estimated)
- Study completion
- 30 Dec 2027 (estimated)
- First posted
- 24 Jan 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a randomized, controlled clinical trial to assess the effects of the ketogenic diet in combination with treatment as usual on brain energy metabolism and psychiatric symptoms in individuals with first episode bipolar disorder and schizoaffective disorder.
Detailed description
Several lines of evidence show energy metabolism and redox dysregulation in bipolar disorder and psychotic disorders. Ketogenic interventions targeting energy metabolism are promising therapeutic approaches to improve mood and psychosis in bipolar disorder and other psychotic disorders. Early intervention is also critical to helping people achieve their goals for recovery after a first episode. Investigators aim to use multimodal imaging and metabolic measures to study the effects of a ketogenic diet intervention on energy metabolism and psychiatric symptoms in individuals with first episode bipolar disorder and schizoaffective disorder. This 12-week randomized controlled trial will assess the benefits of a ketogenic diet in combination with treatment as usual compared to a standard diet. Investigators will measure the effects of nutritional ketosis on brain redox and energy metabolism and other neurometabolic markers using magnetic resonance spectroscopy. Furthermore, investigators will measure the effects of the ketogenic diet on mood and psychotic symptoms and metabolic measures such as insulin resistance.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ketogenic diet arm | Active comparator | Other: Ketogenic dietEligible participants assigned to the ketogenic diet arm will be asked to follow the ketogenic diet (KD) for 12 weeks in addition to any ongoing medications (e.g., mood stabilizers and/or second-generation antipsychotics). Participants will receive weekly and as needed diet counseling from a registered dietician. Participants will be asked to monitor and report their blood ketone levels each day via a finger-prick device provided by the study team. Participants have the ability to opt into an optional open label phase where they can continue on the ketogenic diet with the daily finger pricks for another 12 weeks after the 12-week main study. |
| Dietary Guidelines for Americans arm | Active comparator | Other: Dietary Guidelines for AmericansEligible participants assigned to the Dietary Guidelines for Americans (DGA) arm will adhere to the Dietary Guidelines for Americans in addition to any ongoing medications (e.g., mood stabilizers and/or second-generation antipsychotics). Participants will receive weekly and as needed diet counseling from a registered dietician. Participants will be asked to monitor and report their blood ketone levels each day via a finger-prick device provided by the study team. Participants have the ability to opt into an optional open label phase where they can switch to the ketogenic diet with the daily finger pricks for 12 weeks after the 12-week main study. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Between the ages of 18 and 45.
- Ability to adhere to study diets.
- Diagnostic and Statistical Manual of Mental Disorders-5 (DSM-5) diagnosis of bipolar I disorder or schizoaffective disorder with onset of illness in the last 7 years.
- Must have a stable psychiatric disorder with no change in psychiatric medications within the past 2 weeks of screening
- Must not be expected to require addition of any new psychiatric medications during the 12-week duration of the study.
Key exclusion criteria (13 listed)
- Unable to sign informed consent
- Contraindication to magnetic resonance (MR) scan (including claustrophobia)
- Unstable medical illness (including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease)
- Current DSM-5 substance use disorder
- Currently pregnant, nursing, or of childbearing potential and not using a medically accepted means of contraception
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketogenic dietThe ketogenic diet (KD) is a normo-caloric diet composed of high-fat, low carbohydrate, and adequate protein intake. The KD will consist of 3 meals a day plus snacks, targeting 75-80% fat, 13-18% protein, 7% carbohydrates. | Other | Ketogenic diet arm |
| Dietary Guidelines for AmericansDietary Guidelines for Americans diet is a normo-caloric diet consisting of 3 meals a day plus snacks, emphasizing nutrient dense foods to meet food group needs (85% of calories), and limits foods and beverages higher in added sugars and saturated fat (15% of calories). | Other | Dietary Guidelines for Americans arm |
Primary outcome
Change in brain redox nicotinamide adenine dinucleotide metabolites ratio (NAD+/NADH)
Time frame: 12 weeks
Change from baseline to week 12 in NAD+/NADH as measured by in vivo phosphorus magnetic resonance spectroscopy (31P-MRS).
Change in brain creatine kinase forward reaction rate (kf)
Time frame: 12 weeks
Change from baseline to week 12 in creatine kinase forward reaction rate (kf) as measured by 31P magnetization transfer (MT) MRS.
Change in insulin resistance
Time frame: 12 weeks
Change from baseline to week 12 of insulin resistance measured using the homeostatic model assessment of insulin resistance (HOMA-IR) using fasting blood glucose and insulin levels.
Change in psychotic symptoms
Time frame: 12 weeks
Change from baseline to week 12 in Positive and Negative Syndrome Scale (PANSS) total score. Scores range from 30-210; a higher score indicates a higher level of psychotic symptoms.
Change in depressive symptoms
Time frame: 12 weeks
Change from baseline to week 12 in Hamilton Rating Scale for Depression (HAM-D) total score. Scores range from 0-52; a higher score indicates a higher level of depression.
Change in mania symptoms
Time frame: 12 weeks
Change from baseline to week 12 in Young Mania Rating Scale (YMRS) total score. Scores range from 0-60. A higher score indicates a more severe illness.
Change in Clinical Global Impression (CGI) Scale
Time frame: 12 weeks
Change from baseline to week 12 in Clinical Global Impression (CGI) Scale. Scores range from 1-7; a higher score indicates higher severity of illness.
21 secondary outcomes
Change in body weight
Time frame: 12 weeks
Change in glycated hemoglobin (Hemoglobin A1c) level
Time frame: 12 weeks
Change in triglyceride levels
Time frame: 12 weeks
Change in low-density lipoprotein (LDL) levels
Time frame: 12 weeks
Change in high-density lipoprotein (HDL) levels
Time frame: 12 weeks
Change in high-sensitivity C-reactive protein (hs-CRP) levels
Time frame: 12 weeks
Change in brain gamma-aminobutyric acid (GABA) concentration
Time frame: 12 weeks
Change in brain glutamate metabolite concentration
Time frame: 12 weeks
Change in brain glutathione (GSH)
Time frame: 12 weeks
Change in brain Phosphocreatine (PCr)
Time frame: 12 weeks
Change in brain pH
Time frame: 12 weeks
Change in brain inorganic phosphate concentration
Time frame: 12 weeks
Change in adverse events
Time frame: 12 weeks
Change in anxiety symptoms
Time frame: 12 weeks
Change in stress symptoms
Time frame: 12 weeks
Change in cognitive performance
Time frame: 12 weeks
Change in Global Functioning Scale (GFS) - Social and Role total score
Time frame: 12 weeks
Change in cell-free mitochondrial DNA (cf-mtDNA)
Time frame: 12 weeks
Change in growth differentiation factor 15 (GDF15)
Time frame: 12 weeks
Change in blood NAD/NADH+ ratio
Time frame: 12 weeks
Change in blood GSH/GSSH ratio
Time frame: 12 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Aug 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Virginie-Anne Chouinard, MD contact
Virginie-Anne Chouinard, MD principal investigator
Mclean Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ketogenic diet and Dietary Guidelines for Americans in people with Bipolar I Disorder and Psychosis, run by Mclean Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 17 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kaitlin Shannon, B.A. (617-855-2410, kshannon6@mgb.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in brain redox nicotinamide adenine dinucleotide metabolites ratio (NAD+/NADH) (time frame: 12 weeks). The study lists 7 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Aug 2026.