Ketogenic Diet for Psychotic Disorders (PsyDiet)

• ClinicalTrials.gov Identifier: NCT03873922
• Recruitment Status: Recruiting
• First Posted: March 14, 2019
• Last Update Posted: September 16, 2021
• Sponsor: Kuopio University Hospital
• Collaborator: Deakin University
• Information provided by (Responsible Party): Kuopio University Hospital

Study Description

Brief Summary:

Disturbances in glucose metabolism and glutamate neurotransmission feature in the pathophysiology of psychotic disorders. Ketogenic diet (KD) is a high-fat, low-carbohydrate diet that restricts glucose and forces metabolism of ketones, which serve as alternative energy substrates for the brain. KD is an established treatment for intractable epilepsy. However, we lack the randomized controlled trials (RCT) evidence regarding potential effects of KD on psychotic symptoms in humans.

This randomised, controlled pilot study aims to investigate:

1. feasibility of a Modified Ketogenic Diet (MKD) intervention protocol in psychotic inpatients,
2. potential impact of MKD intervention on psychotic symptoms, depressive and anxiety symptoms, and functioning in patients with psychotic symptoms / psychotic disorder.

A 6-week randomised KD pilot study will be carried out in psychotic inpatients (aimed n=40) at Kuopio University Hospital, Finland. In the KD group, carbohydrate consumption is limited to 15-20 g/day to activate ketosis. The control group will have their ordinary hospital meals. A number of different assessment will be carried out at time points 0, 1 week, 3 weeks and 6 weeks.

Condition or disease	Intervention/treatment	Phase
Psychosis; Acute; Psychosis; Psychotic Disorders; Schizophrenia	Other: Ketogenic diet intervention	Not Applicable

Detailed Description:

Disturbances in glucose metabolism and glutamate neurotransmission feature in the pathophysiology of psychotic disorders. Ketogenic diet (KD) is a high-fat, low-carbohydrate diet that restricts glucose and forces metabolism of ketones, which serve as alternative energy substrates for the brain. KD is an established treatment for intractable epilepsy. However, we lack the RCT evidence regarding potential effects of KD on psychotic symptoms in humans.

This randomised, controlled pilot study aims to investigate:

1. feasibility of a Modified Ketogenic Diet (MKD) intervention protocol in psychotic inpatients,
2. potential impact of MKD intervention on psychotic symptoms, depressive and anxiety symptoms, and functioning in patients with psychotic symptoms / psychotic disorder.

A 6-week randomised KD pilot study will be carried out in psychotic inpatients (aimed n=40) at Kuopio University Hospital, Finland. In the KD group, carbohydrate consumption is limited to 15-20 g/day to activate ketosis. The control group will have their ordinary hospital meals. The Structured Clinical Interview for DSM Axis I disorders (SCID-I), and the Positive and Negative Syndrome Scale (PANSS) will assess current psychotic disorders and psychotic symptoms, respectively. Blood glucose, lipid, and ketone body levels, and weight will be measured. Background variables (socioeconomic factors, comorbidities, obtained treatments including medications, and health behaviours including diet) will be documented.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: After baseline examinations, participants will be randomized to receive either ketogenic meals or conventional hospital meals during the study (maximum of six weeks). Otherwise treatment as usual.
• Masking: Double (Investigator, Outcomes Assessor)
• Masking Description: Blinded research assistant will carry out the PANSS assessment and do the SCID-interviews. Another research assistant will conduct the other measurements (including anthropometry). Care provider will order the meals for the participants, according to the randomization of the patients.
• Primary Purpose: Treatment
• Official Title: Dietary Intervention for Psychotic Disorders: a Pilot Intervention Study of Ketogenic Diet for Psychotic Symptoms - PsyDiet Pilot Study
• Actual Study Start Date: March 15, 2021
• Estimated Primary Completion Date: December 31, 2022
• Estimated Study Completion Date: January 31, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: Ketogenic diet intervention; Ketogenic meals will be offered for the participants during the trial.	Other: Ketogenic diet intervention; Ketogenic, really low carbohydrate containing (15-20 g/day), meals will be offered to the participants.; Other Names: KD; Modified Ketogenic Diet
No Intervention: Control group; Conventional hospital meals as usual will be offered during the trial.

Outcome Measures

Primary Outcome Measures :

1. The change in Positive and Negative Syndrome Scale (PANSS) total score from baseline to 6 weeks. [ Time Frame: The change from baseline to the end of the intervention (6 weeks) OR if discharged earlier, from baseline to the latest study assessment time point (1 or 3 weeks) ]
   Change in positive and negative psychotic symptoms, assessed at time points baseline, 1, 3 and 6 weeks. The participants are rated from 1 to 7 on 30 different symptoms based on the interview. PANSS Total score minimum is 30, maximum is 210. As 1 rather than 0 is given as the lowest score for each item, a participant can not score lower than 30 for the total PANSS score. Scores are given separately for the positive items, negative items, and general psychopathology scales which altogether (summarized) create a total PANSS score. Higher values represent a worse outcome.
2. Feasibility 1, defined by modified ketogenic diet related experiences, challenges and potential adverse effects during the intervention [ Time Frame: Potential adverse effects during the entire trial will be evaluated (from baseline to 1, 3 and 6 weeks), as observed adverse effects may vary between study time points and status of ketosis ]
   Feasibility will be assessed by modified ketogenic diet related experiences, challenges and potential adverse effects by a Questionnaire of potential side effects and acceptance of MKD during the trial.
3. Feasibility 2, defined by percentage of study participants who discontinue diet and percentage of participants reaching ketosis (measured by blood ketone body levels) [ Time Frame: Percentage of participants reaching ketosis and staying in ketosis in the MKD group will be calculated at each time point (weeks 1, 3 and 6) ]
   We will screen blood ketone body levels daily (MKD participants) or weekly (control participants). If participants in the MKD arm are not able to adhere to MKD, they will not reach ketosis or will not stay in ketosis. Feasibility will be defined by percentage of study participants reaching ketosis in the MKD group. In addition, drop-out rate of participants in each study arm will be calculated.

Secondary Outcome Measures :

1. The change in Beck Depression Inventory (BDI) score from baseline to 6 weeks. [ Time Frame: Change in BDI score from baseline to 6 weeks OR if discharged earlier, from baseline to the latest study assessment time point (3 weeks) ]
   Change in depressive symptoms assessed by Beck Depression Inventory scores. BDI is a series of questions developed to measure the intensity, severity, and depth of depression in patients with psychiatric diagnoses. It is composed of 21 questions, each designed to assess a specific symptom. each with four possible responses. Each response is assigned a score ranging from zero to three, indicating the severity of the symptom. Score range is 0-63. Higher values represent a worse outcome.
2. The change in Beck Anxiety Inventory (BAI) score from baseline to 6 weeks [ Time Frame: Change in BAI score from baseline to 6 weeks OR if discharged earlier, from baseline to the latest study assessment time point (3 weeks) ]
   Change in anxiety symptoms assessed by BAI scores. BAI evaluates both physiological and cognitive symptoms of anxiety and item overlap with other self report depression inventories is minimised. The BAI consists of 21 items; each item is descriptive of a symptom of anxiety and is rated on a scale of 0 to 3. Thus, the score range is from 0 to 63. Higher values represent a worse outcome.
3. The change in Structured Clinical Interview for DSM Axis I disorders (SCID-I) diagnosis from baseline to 6 weeks [ Time Frame: Change in SCID-I diagnosis from baseline to 6 weeks ]
   The Structured Clinical Interview for DSM Axis I disorders assessing psychotic symptoms (SCID-I) is a validated semi-structured clinical interview (the gold standard tool for psychiatric assessment in a research setting). SCID-I will be used to assess for past and current psychotic disorders at the beginning and at the 6 week of intervention.
4. The change in the Global Assessment of Functioning score from baseline to 6 weeks. [ Time Frame: Change in GAF score from baseline to 6 weeks OR if discharged earlier, from baseline to the latest study assessment time point (1 or 3 weeks) ]
   Change in The Global Assessment of Functioning (GAF). GAF interview will be conducted at each study time point (baseline, 1, 3 and 6 weeks). GAF scale is used to rate how serious a mental illness may be. It measures how much a person's symptoms affect his or her day-to-day life on a scale of 0 to 100. Higher values represent a worse outcome.

Other Outcome Measures:

1. Change in Blood lipid levels [ Time Frame: Change in blood lipids between baseline and 6 weeks ]
   Change in measurements of blood lipids (fP-Kol, fP-KOL-LDL, fP-KOL-HDL, fP-Trigly)
2. Change in Fasting glucose levels [ Time Frame: Change in blood lipids between baseline and 6 weeks ]
   Change in measurement of fasting glucose
3. Change in weight/body mass index (BMI) from baseline to 6 weeks [ Time Frame: Change in weight/BMI from baseline to 6 weeks OR if discharged earlier, from baseline to the latest study assessment time point (1 or 3 weeks) ]
   Change in measured weight/BMI
4. Change in blood pressure (diastolic and systolic) from baseline to 6 weeks. [ Time Frame: Change in blood pressure from baseline to 6 weeks OR if discharged earlier, from baseline to the latest study assessment time point (3 weeks) ]
   Change in blood pressure (diastolic and systolic)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• ≥ 18 years old patient with psychotic symptoms / diagnosed psychotic disorder (ICD-10 diagnoses F20-F29)

Exclusion Criteria:

• BMI <18.5
• Diabetes mellitus (with or without insulin treatment)
• Inability to provide informed consent or to participate due to acute medical conditions, such as severe and acute psychotic symptoms or acute suicidality
• Impairments in vision, audition or immobility
• Pregnancy
• Diagnosed current eating disorder
• Diagnosed Inflammatory Bowel Disease (IBD)
• Severe alcohol or substance abuse
• Decompensated cardial insufficiency
• Infrequent/rare metabolic disorders, such as porphyria, disturbances in fatty acid oxidation or deficiency of CTT1, CPTII, carnitine or pyruvate carboxylase

Contacts and Locations

Contacts

Contact: Anu Ruusunen, PhD; +358407085221; anu.ruusunen@kuh.fi

Contact: Felice Jacka, Professor; felicejacka@gmail.com

Locations

Finland

Kuopio University Hospital, Department of Psychiatry; Recruiting

Kuopio, Finland

Contact: Anu Ruusunen, PhD

Sponsors and Collaborators

Kuopio University Hospital

Deakin University

Investigators

• Principal Investigator: Anu Ruusunen, PhD; Kuopio University Hospital

More Information

• Responsible Party: Kuopio University Hospital
• ClinicalTrials.gov Identifier: NCT03873922
• Other Study ID Numbers: KUH5703458
• First Posted: March 14, 2019
• Last Update Posted: September 16, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Undecided
• Plan Description: Will be decided shortly.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Kuopio University Hospital:

Ketogenic diet; Intervention; Ketosis; Feasibility; Psychosis; Psychotic symptoms; Schizophrenia; Dietary intervention

Additional relevant MeSH terms:

Schizophrenia; Psychotic Disorders; Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders