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Open Label Extension Study of NCT06221852

Not Applicable
Conditions
Bipolar I Disorder
Schizoaffective Disorder
Psychosis
Interventions
Other: Ketogenic diet
Registration Number
NCT06558201
Lead Sponsor
Mclean Hospital
Brief Summary

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

Detailed Description

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.

Recruitment & Eligibility

Status
ENROLLING_BY_INVITATION
Sex
All
Target Recruitment
50
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Ketogenic dietKetogenic dietParticipants 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 diet counseling from a registered dietitian. Participants will be asked to monitor and report their blood ketone and glucose levels each day via a finger-prick device provided by the study team.
Primary Outcome Measures
NameTimeMethod
Change in depressive symptoms24 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.

Change in brain redox nicotinamide adenine dinucleotide metabolites ratio (NAD+/NADH)24 weeks

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

Change in psychotic symptoms24 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.

Change in Clinical Global Impression (CGI) Scale24 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.

Change in brain creatine kinase forward reaction rate (kf)24 weeks

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

Change in mania symptoms24 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.

Change in insulin resistance24 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.

Secondary Outcome Measures
NameTimeMethod
Change in blood GSH/GSSH ratio24 weeks

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

Change in high-sensitivity C-reactive protein (hs-CRP) levels24 weeks

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

Change in high-density lipoprotein (HDL) levels24 weeks

Change from baseline to week 24 in fasting HDL levels

Change in brain glutathione (GSH)24 weeks

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

Change in brain pH24 weeks

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

Change in glycated hemoglobin (Hemoglobin A1c) level24 weeks

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

Change in brain glutamate metabolite concentration24 weeks

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

Change in stress symptoms24 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.

Change in low-density lipoprotein (LDL) levels24 weeks

Change from baseline to week 24 in fasting LDL levels

Change in brain gamma-aminobutyric acid (GABA) concentration24 weeks

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

Change in brain Phosphocreatine (PCr)24 weeks

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

Change in anxiety symptoms24 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.

Change in body weight24 weeks

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

Change in triglyceride levels24 weeks

Change from baseline to week 24 in fasting triglyceride levels.

Change in brain inorganic phosphate concentration24 weeks

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

Change in adverse events24 weeks

Change from baseline to week 24 in adverse events.

Change in cognitive performance24 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.

Change in Global Functioning Scale (GFS) - Social and Role total score24 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.

Change in blood NAD/NADH+ ratio24 weeks

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

Change in growth differentiation factor 15 (GDF15)24 weeks

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

Change in cell-free mitochondrial DNA (cf-mtDNA)24 weeks

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

Trial Locations

Locations (1)

McLean Hospital

🇺🇸

Belmont, Massachusetts, United States

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