ObesityNCT03935854
Impact of a Ketogenic Diet on Metabolic and Psychiatric Health in Patients With Bipolar or Schizophrenia Illness
A study testing LCHF, Ketogenic Diet in people with Obesity and Ketogenic Dieting, run by Stanford University at 1 site in United States.
Trial summary
To initiate a low-carbohydrate, high-fat (LCHF) or ketogenic dietary (KD) intervention among a cohort of outpatients with either schizophrenia or bipolar illness who also have metabolic abnormalities, overweight/obesity, and/or are currently taking psychotropic medications experiencing metabolic side effects. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Obesity, Ketogenic Dieting, Metabolic Syndrome
- What is being tested?
- LCHF, Ketogenic Diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Feb 2019to 11 Aug 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-75 years old
- Meet DSM V criteria for schizophrenia or bipolar disorder, any subtype, for > 1 year and clinically stable (with no hospitalization for past 3 months)
- Currently taking psychotropic medication and gained at least 5% weight since starting medication or have a BMI greater than or equal to 26 kg/m2 or presence of at least one metabolic abnormality (hypertriglyceridemia, insulin resistance, dyslipidemia, impaired glucose tolerance)
- Willing to consent to all study procedures and attend follow-up appointments and motivated to follow the dietary program.
- Sufficient control over their food intake to adhere to study diets.
- Willingness to regularly monitor blood pressure, glucose, dietary intake, and body weight over the 4-month trial
Who cannot join
- Any subject pregnant or nursing
- Comorbidity of developmental delay
- Active substance abuse with illicit drugs or alcohol
- In a current severe mood or psychotic state when entering the study that would prohibit compliance with study visits or dietary program.
- Anyone who has been hospitalized or taken clozapine over the past 3 months
- Inability to complete baseline measurements
Show all 14Show fewer
- Severe renal or hepatic insufficiency
- Cardiovascular dysfunction, including diagnosis of:
- Congestive heart failure
- Angina
- Arrhythmias
- Cardiomyopathy
- Valvular heart disease
- Any other medical condition that may make either diet dangerous as determined by the study medical team (e.g. anorexia nervosa)
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University Department of Psychiatry & Behavioral Sciences
Stanford, California, 94305
About this study
Official title: Impact of A Low-Carbohydrate, High-Fat, Ketogenic Diet on Obesity, Metabolic Abnormalities and Psychiatric Symptoms in Patients With Bipolar or Schizophrenia Illness: A Pilot Trial
To initiate a low-carbohydrate, high-fat (LCHF) or ketogenic dietary (KD) intervention among a cohort of outpatients with either schizophrenia or bipolar illness who also have metabolic abnormalities, overweight/obesity, and/or are currently taking psychotropic medications experiencing metabolic side effects.
Read the detailed description
Adults with mental illness represent a high-risk, marginalized group in the current metabolic and obesity epidemic. Among US adults with severe mental illness, metabolic syndrome are highly prevalent conditions having severe consequences, with patients estimated to die on average 25 years earlier than the general population largely of premature cardiovascular disease. Many psychiatric medications, particularly neuroleptics and mood stabilizers, may, in addition, contribute to metabolic side effects and weight gain. Low-carbohydrate high-fat (LCHF) or ketogenic diets (KD) have been shown to reduce cardiovascular risk in those with insulin resistance. Recent findings support the idea that bipolar disorder, along with other psychiatric diseases schizophrenia, may have roots of metabolic dysfunction: cerebral glucose hypometabolism, oxidative stress, as well as mitochondrial and neurotransmitter dysfunction which has downstream effects on synapse connections. A KD diet provides alternative fuel to the brain aside from glucose and is believed to contain beneficial neuroprotective effects, including stabilization of brain networks, reduction of inflammation and oxidative stress. The purpose of this study is to evaluate both the metabolic and psychiatric outcomes with a KD diet in this psychiatric population.
- Conditions
- Obesity, Ketogenic Dieting, Metabolic Syndrome, Bipolar Disorder, Schizophrenia, Weight Gain
- Being tested
- LCHF, Ketogenic Diet
- Medical subject headings
- Obesity, Metabolic Syndrome, Bipolar Disorder, Schizophrenia, Weight Gain, Brain Diseases, Metabolic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LCHF, Ketogenic DietOther
Low Carbohydrate, Moderate Protein, High Fat Ketogenic Dietary Intervention 16 weeks
| Study group | Role | What they receive |
|---|---|---|
| Ketogenic Diet 16 Week Group | Experimental | Patients follow ketogenic diet for 16 weeks, with monitoring of physical and psychological health and coaching support Receives: Other: LCHF, Ketogenic Diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in heart rate from baseline
Heart rate recorded at 9 visits during study
Measured: Baseline, 16 weeks
Change in blood pressure from baseline
Blood pressure recorded at 9 visits during study
Measured: Baseline, 16 weeks
Change in weight from baseline
Weight recorded at 9 visits during study
Measured: Baseline, 16 weeks
Change in waist circumference from baseline
waist circumference measured at 9 visits during study
Measured: Baseline, 16 weeks
Change in visceral fat mass from baseline
Body composition (SECA) recorded at 5 visits during study
Measured: Baseline, 16 weeks
Change in body fat mass from baseline
Body composition (SECA) recorded at 5 visits during study
Measured: Baseline, 16 weeks
Percent Change in Hemoglobin A1c from baseline
Hemoglobin A1c recorded at initial and final visits
Measured: Baseline, 16 weeks
Change in insulin resistance measure (HOMA-IR) from baseline
HOMA-IR measured at initial and final visits
Measured: Baseline, 16 weeks
Change in inflammatory marker (hsCRP) from baseline
hsCRP measured at initial and final visits
Measured: Baseline, 16 weeks
Change in lipid profile TG (triglycerides) from baseline
Lipid profile TG measured at initial and final visits
Measured: Baseline, 16 weeks
Change in lipid profile small LDL (small dense LDL) from baseline
Lipid profile small LDL measured at initial and final visits
Measured: Baseline, 16 weeks
Change in lipid profile (HDL) from baseline
Lipid profile HDL measured at initial and final visits
Measured: Baseline,16 weeks
Secondary outcomes (8)
Psychiatric Indices - Mood
Change in Mood Qualitative Score (Clinical Mood Monitoring) from baseline
Measured: Baseline, 16 weeks
Psychiatric Indices- Clinical Global Impression
Change in Clinical Global Impression Scales (CGI) from baseline 1-7 scale. 1= not at all ill, 7= among the most extremely ill patients)
Measured: Baseline, 16 weeks
Generalized Anxiety Disorder - GAD-7 Anxiety
Change in Generalized Anxiety Symptom (GAD-7) scale from baseline. 0-15+ scale. (0= no anxiety, 15+= severe anxiety)
Measured: Baseline, 16 weeks
Patient Health Questionnaire - PHQ-9 Depression
Change in Patient Health Questionnaire (PHQ-9) from baseline. Score range 0-27 (0= no depression, 27= severe depression)
Measured: Baseline, 16 weeks
Psychiatric Indices- Global Assessment of Functioning
Change in Global Assessment of Functioning (GAF) Scale from baseline. 1-100 scale (1= persistent danger of hurting self or others, 100= superior functioning)
Measured: Baseline, 16 weeks
Psychiatric Indices- Quality of Life
Change in Manchester Quality of Life Scale (MANSA) from baseline. Range 12-84 (each of 12 outcomes rated from 1= could not be worse to 7= could not be better; <4= dissatisfied with QoL, >4= satisfied with QoL)
Measured: Baseline, 16 weeks
Psychiatric Indices- BPRS
Change in Brief Psychiatric Rating Scale (BPRS) from baseline. Score range 18-126. (For each of 18 symptoms, 1=symptom not present, 7= extremely severe)
Measured: Baseline, 16 weeks
Pittsburgh Sleep Quality Index - PSQI
Change in Pittsburgh Sleep Quality Index from baseline. 0-21 scale (<5=good sleeper; 5+= meaningfully disturbed sleep or poor sleeper)
Measured: Baseline, 16 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2019
- Study start13 Feb 2019
- Primary completion11 Aug 2022
- Study completion11 Aug 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Shebani Sethi, Stanford University
- Investigators
- Shebani Sethi, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03935854
- Sponsor's protocol ID
- 48527
- Status last verified
- Dec 2024
- First submitted
- 30 Apr 2019
- Last updated
- 17 Dec 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Sethi S, Sinha A, Gearhardt AN. Low carbohydrate ketogenic therapy as a metabolic treatment for binge eating and ultraprocessed food addiction. Curr Opin Endocrinol Diabetes Obes. 2020 Oct;27(5):275-282. doi: 10.1097/MED.0000000000000571.
PubMed 32773576Carmen M, Safer DL, Saslow LR, Kalayjian T, Mason AE, Westman EC, Sethi S. Treating binge eating and food addiction symptoms with low-carbohydrate Ketogenic diets: a case series. J Eat Disord. 2020 Jan 29;8:2. doi: 10.1186/s40337-020-0278-7. eCollection 2020.
PubMed 32010444Norwitz NG, Sethi S, Palmer CM. Ketogenic diet as a metabolic treatment for mental illness. Curr Opin Endocrinol Diabetes Obes. 2020 Oct;27(5):269-274. doi: 10.1097/MED.0000000000000564.
PubMed 32773571Yu B, Ozveren R, Sethi Dalai S. Ketogenic diet as a metabolic therapy for bipolar disorder: Clinical developments. Submitted to Journal of Affective Disorders. Research Square preprint March 2020: DOI is: 10.21203/rs.3.rs-334453/v1
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.
PubMed 30075165Sarnyai Z, Kraeuter AK, Palmer CM. Ketogenic diet for schizophrenia: clinical implication. Curr Opin Psychiatry. 2019 Sep;32(5):394-401. doi: 10.1097/YCO.0000000000000535.
PubMed 31192814Sethi S, Wakeham D, Ketter T, Hooshmand F, Bjornstad J, Richards B, Westman E, Krauss RM, Saslow L. Ketogenic Diet Intervention on Metabolic and Psychiatric Health in Bipolar and Schizophrenia: A Pilot Trial. Psychiatry Res. 2024 May;335:115866. doi: 10.1016/j.psychres.2024.115866. Epub 2024 Mar 20.
PubMed 38547601
Study at a glance
From the registry record, last updated by the sponsor on 17 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of A Low-Carbohydrate, High-Fat, Ketogenic Diet on Obesity, Metabolic Abnormalities and Psychiatric Symptoms in Patients With Bipolar or Schizophrenia Illness: A Pilot Trial
- ClinicalTrials.gov ID
- NCT03935854
- Acronym / sponsor ID
- 48527
- Conditions
- Obesity, Ketogenic Dieting, Metabolic Syndrome, Bipolar Disorder, Schizophrenia, Weight Gain
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- 13 Feb 2019 (actual)
- Primary completion
- 11 Aug 2022 (actual)
- Study completion
- 11 Aug 2022 (actual)
- First posted
- 2 May 2019 (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.
To initiate a low-carbohydrate, high-fat (LCHF) or ketogenic dietary (KD) intervention among a cohort of outpatients with either schizophrenia or bipolar illness who also have metabolic abnormalities, overweight/obesity, and/or are currently taking psychotropic medications experiencing metabolic side effects.
Detailed description
Adults with mental illness represent a high-risk, marginalized group in the current metabolic and obesity epidemic. Among US adults with severe mental illness, metabolic syndrome are highly prevalent conditions having severe consequences, with patients estimated to die on average 25 years earlier than the general population largely of premature cardiovascular disease. Many psychiatric medications, particularly neuroleptics and mood stabilizers, may, in addition, contribute to metabolic side effects and weight gain. Low-carbohydrate high-fat (LCHF) or ketogenic diets (KD) have been shown to reduce cardiovascular risk in those with insulin resistance. Recent findings support the idea that bipolar disorder, along with other psychiatric diseases schizophrenia, may have roots of metabolic dysfunction: cerebral glucose hypometabolism, oxidative stress, as well as mitochondrial and neurotransmitter dysfunction which has downstream effects on synapse connections. A KD diet provides alternative fuel to the brain aside from glucose and is believed to contain beneficial neuroprotective effects, including stabilization of brain networks, reduction of inflammation and oxidative stress. The purpose of this study is to evaluate both the metabolic and psychiatric outcomes with a KD diet in this psychiatric population.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Ketogenic Diet 16 Week Group | Experimental | Other: LCHF, Ketogenic DietPatients follow ketogenic diet for 16 weeks, with monitoring of physical and psychological health and coaching support |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age 18-75 years old
- Meet DSM V criteria for schizophrenia or bipolar disorder, any subtype, for > 1 year and clinically stable (with no hospitalization for past 3 months)
- Currently taking psychotropic medication and gained at least 5% weight since starting medication or have a BMI greater than or equal to 26 kg/m2 or presence of at least one metabolic abnormality (hypertriglyceridemia, insulin resistance, dyslipidemia, impaired glucose tolerance)
- Willing to consent to all study procedures and attend follow-up appointments and motivated to follow the dietary program.
- Sufficient control over their food intake to adhere to study diets.
Key exclusion criteria (14 listed)
- Any subject pregnant or nursing
- Comorbidity of developmental delay
- Active substance abuse with illicit drugs or alcohol
- In a current severe mood or psychotic state when entering the study that would prohibit compliance with study visits or dietary program.
- Anyone who has been hospitalized or taken clozapine over the past 3 months
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 |
|---|---|---|
| LCHF, Ketogenic DietLow Carbohydrate, Moderate Protein, High Fat Ketogenic Dietary Intervention 16 weeks | Other | Ketogenic Diet 16 Week Group |
Primary outcome
Change in heart rate from baseline
Time frame: Baseline, 16 weeks
Heart rate recorded at 9 visits during study
Change in blood pressure from baseline
Time frame: Baseline, 16 weeks
Blood pressure recorded at 9 visits during study
Change in weight from baseline
Time frame: Baseline, 16 weeks
Weight recorded at 9 visits during study
Change in waist circumference from baseline
Time frame: Baseline, 16 weeks
waist circumference measured at 9 visits during study
Change in visceral fat mass from baseline
Time frame: Baseline, 16 weeks
Body composition (SECA) recorded at 5 visits during study
Change in body fat mass from baseline
Time frame: Baseline, 16 weeks
Body composition (SECA) recorded at 5 visits during study
Percent Change in Hemoglobin A1c from baseline
Time frame: Baseline, 16 weeks
Hemoglobin A1c recorded at initial and final visits
Change in insulin resistance measure (HOMA-IR) from baseline
Time frame: Baseline, 16 weeks
HOMA-IR measured at initial and final visits
Change in inflammatory marker (hsCRP) from baseline
Time frame: Baseline, 16 weeks
hsCRP measured at initial and final visits
Change in lipid profile TG (triglycerides) from baseline
Time frame: Baseline, 16 weeks
Lipid profile TG measured at initial and final visits
Change in lipid profile small LDL (small dense LDL) from baseline
Time frame: Baseline, 16 weeks
Lipid profile small LDL measured at initial and final visits
Change in lipid profile (HDL) from baseline
Time frame: Baseline,16 weeks
Lipid profile HDL measured at initial and final visits
8 secondary outcomes
Psychiatric Indices - Mood
Time frame: Baseline, 16 weeks
Psychiatric Indices- Clinical Global Impression
Time frame: Baseline, 16 weeks
Generalized Anxiety Disorder - GAD-7 Anxiety
Time frame: Baseline, 16 weeks
Patient Health Questionnaire - PHQ-9 Depression
Time frame: Baseline, 16 weeks
Psychiatric Indices- Global Assessment of Functioning
Time frame: Baseline, 16 weeks
Psychiatric Indices- Quality of Life
Time frame: Baseline, 16 weeks
Psychiatric Indices- BPRS
Time frame: Baseline, 16 weeks
Pittsburgh Sleep Quality Index - PSQI
Time frame: Baseline, 16 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Dec 2024.
- Background: PubMed 32773576Sethi S, Sinha A, Gearhardt AN. Low carbohydrate ketogenic therapy as a metabolic treatment for binge eating and ultraprocessed food addiction. Curr Opin Endocrinol Diabetes Obes. 2020 Oct;27(5):275-282. doi: 10.1097/MED.0000000000000571.
- Background: PubMed 32010444Carmen M, Safer DL, Saslow LR, Kalayjian T, Mason AE, Westman EC, Sethi S. Treating binge eating and food addiction symptoms with low-carbohydrate Ketogenic diets: a case series. J Eat Disord. 2020 Jan 29;8:2. doi: 10.1186/s40337-020-0278-7. eCollection 2020.
- Background: PubMed 32773571Norwitz NG, Sethi S, Palmer CM. Ketogenic diet as a metabolic treatment for mental illness. Curr Opin Endocrinol Diabetes Obes. 2020 Oct;27(5):269-274. doi: 10.1097/MED.0000000000000564.
- BackgroundYu B, Ozveren R, Sethi Dalai S. Ketogenic diet as a metabolic therapy for bipolar disorder: Clinical developments. Submitted to Journal of Affective Disorders. Research Square preprint March 2020: DOI is: 10.21203/rs.3.rs-334453/v1
- Background: PubMed 30075165Brietzke 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.
- Background: PubMed 31192814Sarnyai Z, Kraeuter AK, Palmer CM. Ketogenic diet for schizophrenia: clinical implication. Curr Opin Psychiatry. 2019 Sep;32(5):394-401. doi: 10.1097/YCO.0000000000000535.
- Results publication: PubMed 38547601Sethi S, Wakeham D, Ketter T, Hooshmand F, Bjornstad J, Richards B, Westman E, Krauss RM, Saslow L. Ketogenic Diet Intervention on Metabolic and Psychiatric Health in Bipolar and Schizophrenia: A Pilot Trial. Psychiatry Res. 2024 May;335:115866. doi: 10.1016/j.psychres.2024.115866. Epub 2024 Mar 20.
- Individual participant dataSharing planned: No
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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. This study is not recruiting at the moment.
Shebani Sethi, MD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing LCHF, Ketogenic Diet in people with Obesity and Ketogenic Dieting, run by Stanford University 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 6 inclusion and 14 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: finished, as of the sponsor's last update on 17 Dec 2024. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in heart rate from baseline (time frame: Baseline, 16 weeks). The study lists 12 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03935854, which also lists 7 linked publications.
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 Dec 2024.