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NCT Number: NCT06558201

Open Label Extension Study of NCT06221852

This is a 12-week open-label extension study for participants completing study NCT06221852.

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Key information

About this study

In this 12-week single arm open label extension study of NCT06221852, the investigators aim to assess the longer term efficacy, safety and tolerability of the ketogenic diet in participants completing the randomized study phase of NCT06221852. Investigators will assess longer term effects on energy metabolism, insulin resistance and psychiatric symptoms.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participants who met original entry criteria in, and completed, the randomized 12-week study of NCT06221852.

Exclusion criteria

-No longer meeting original entry criteria from the randomized 12-week study of NCT06221852.

Treatment and study plan

Ketogenic diet

Other

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.

Other names: Keto diet

Primary outcomes

  1. Change in brain redox nicotinamide adenine dinucleotide metabolites ratio (NAD+/NADH)

    Time frame: 24 weeks

    Change from baseline to week 24 in NAD+/NADH as measured by in vivo phosphorus magnetic resonance spectroscopy (31P-MRS).

  2. Change in brain creatine kinase forward reaction rate (kf)

    Time frame: 24 weeks

    Change from baseline to week 24 in creatine kinase forward reaction rate (kf) as measured by 31P magnetization transfer (MT) MRS.

  3. Change in insulin resistance

    Time frame: 24 weeks

    Change from baseline to week 24 of insulin resistance measured using the homeostatic model assessment of insulin resistance (HOMA-IR) using fasting blood glucose and insulin levels.

  4. Change in psychotic symptoms

    Time frame: 24 weeks

    Change from baseline to week 24 in Positive and Negative Syndrome Scale (PANSS) total score. Scores range from 30-210; a higher score indicates a higher level of psychotic symptoms.

  5. Change in depressive symptoms

    Time frame: 24 weeks

    Change from baseline to week 24 in Hamilton Rating Scale for Depression (HAM-D) total score. Scores range from 0-52; a higher score indicates a higher level of depression.

  6. Change in mania symptoms

    Time frame: 24 weeks

    Change from baseline to week 24 in Young Mania Rating Scale (YMRS) total score. Scores range from 0-60. A higher score indicates a more severe illness.

  7. Change in Clinical Global Impression (CGI) Scale

    Time frame: 24 weeks

    Change from baseline to week 24 in Clinical Global Impression (CGI) Scale. Scores range from 1-7; a higher score indicates higher severity of illness.

Secondary outcomes

  1. Change in body weight

    Time frame: 24 weeks

    Change from baseline to week 24 in participant body weight in kilograms, as measured using a standing scale.

  2. Change in glycated hemoglobin (Hemoglobin A1c) level

    Time frame: 24 weeks

    Change from baseline to week 24 in fasting Hemoglobin A1c level.

  3. Change in triglyceride levels

    Time frame: 24 weeks

    Change from baseline to week 24 in fasting triglyceride levels.

  4. Change in low-density lipoprotein (LDL) levels

    Time frame: 24 weeks

    Change from baseline to week 24 in fasting LDL levels

  5. Change in high-density lipoprotein (HDL) levels

    Time frame: 24 weeks

    Change from baseline to week 24 in fasting HDL levels

  6. Change in high-sensitivity C-reactive protein (hs-CRP) levels

    Time frame: 24 weeks

    Change from baseline to week 24 in fasting hs-CRP levels.

  7. Change in brain gamma-aminobutyric acid (GABA) concentration

    Time frame: 24 weeks

    Change from baseline to week 24 in GABA concentration measured by proton magnetic resonance spectroscopy.

  8. Change in brain glutamate metabolite concentration

    Time frame: 24 weeks

    Change from baseline to week 24 in glutamate metabolite concentration measured by proton magnetic resonance spectroscopy.

  9. Change in brain glutathione (GSH)

    Time frame: 24 weeks

    Change from baseline to week 24 in brain GSH measured by proton magnetic resonance spectroscopy.

  10. Change in brain Phosphocreatine (PCr)

    Time frame: 24 weeks

    Changes from baseline to week 24 in PCr concentration as measured by in vivo 31P-MRS.

  11. Change in brain pH

    Time frame: 24 weeks

    Change from baseline to week 24 in pH as measured by in vivo 31P MRS

  12. Change in brain inorganic phosphate concentration

    Time frame: 24 weeks

    Change from baseline to week 24 in inorganic phosphate (Pi) concentration as measured by in vivo 31P MRS.

  13. Change in adverse events

    Time frame: 24 weeks

    Change from baseline to week 24 in adverse events.

  14. Change in anxiety symptoms

    Time frame: 24 weeks

    Change from baseline to week 24 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.

  15. Change in stress symptoms

    Time frame: 24 weeks

    Change from baseline to week 24 in Depression Anxiety Stress Scales (DASS-42) Stress Subscale score. Scores range from 0-42; a higher score indicates a higher level of stress.

  16. Change in cognitive performance

    Time frame: 24 weeks

    Change from baseline to week 24 in Matrics Consensus Cognitive Battery (MCCB) Total Score. Scores range from 0.00% - 100.00%; a higher score indicates higher cognition.

  17. Change in Global Functioning Scale (GFS) - Social and Role total score

    Time frame: 24 weeks

    Change from baseline to week 24 in Global Functioning Scale (GFS) - Social and Role total score. Scores range from 6-60; a lower score indicates worse social and role functioning.

  18. Change in blood NAD/NADH+ ratio

    Time frame: 24 weeks

    Change from baseline to week 24 in blood NAD/NADH+ ratio.

  19. Change in blood GSH/GSSH ratio

    Time frame: 24 weeks

    Change from baseline to week 24 in blood GSH/GSSH ratio.

  20. Change in growth differentiation factor 15 (GDF15)

    Time frame: 24 weeks

    Change from baseline to week 24 in blood and saliva GDF15 levels.

  21. Change in cell-free mitochondrial DNA (cf-mtDNA)

    Time frame: 24 weeks

    Change from baseline to week 24 in blood and saliva cf-mtDNA levels.

Other outcomes

  1. Change in World Health Organization Disability Assessment Schedule (WHODAS) score

    Time frame: 24 weeks

    Change from baseline to week 24 in World Health Organization Disability Assessment Schedule (WHODAS) scale. Scores range from 0-144. A higher score indicates greater dysfunction and disability in major life domains.

  2. Change in World Health Organization Quality of Life (WHOQOL) score

    Time frame: 24 weeks

    Change from baseline to week 24 in World Health Organization Quality of Life (WHOQOL) scale. Scores range from 1-130. A lower score indicates lower perceived quality of life.

  3. Change in Extrapyramidal Symptom Rating Scale (ESRS) total score

    Time frame: 24 weeks

    Change from baseline to week 24 in Extrapyramidal Symptom Rating Scale (ESRS) total score. Scores range from 0-102; a higher score indicates more severe symptoms.

  4. Change in Pittsburgh Sleep Quality Index (PSQI) total score

    Time frame: 24 weeks

    Change from baseline to week 24 in Pittsburgh Sleep Quality Index (PSQI) total score. Scores range from 0-21; a higher score indicates worse sleep quality.

  5. Change in resting-state fMRI

    Time frame: 24 weeks

    Change within network positive correlations and between network negative correlations from baseline to week 24.

  6. Change in gray matter volume

    Time frame: 24 weeks

    Change in the gray matter volumes (cubic millimeters) of the frontal, parietal and temporal lobes as defined by Freesurfer's Desikan-Killiany Brain Atlas from baseline to week 24.

  7. Change in cortical surface area

    Time frame: 24 weeks

    Change in the cortical surface area (millimeters squared) of the frontal, parietal and temporal lobes as defined by Freesurfer's Desikan-Killiany Brain Atlas from baseline to week 24.

  8. Change in white matter fractional anisotropy (FA)

    Time frame: 24 weeks

    Change in fractional anisotropy (FA), a scalar measure of diffusivity, of water in the brain assessed by DTI at 3T from baseline to week 24. FA values range from 0 (isotropic, meaning diffusion is equally restricted in 3D space) to 1 (anisotrophic, meaning that diffusion is completely restricted to a single direction).

Sponsors and collaborators

Lead sponsor

Mclean Hospital

Other

Collaborators

  • Baszucki Family Foundation

Registry information

Official study title

Open Label Extension Study of NCT06221852 of the Ketogenic Diet in Participants With First Episode Bipolar Disorder.

Important dates

Study start
2024
Primary completion
2027
Study completion
2027
First posted
Aug 16, 2024
Registry last updated
Jun 25, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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