Clinical trial NCT03873922: Ketogenic Diet for Psychotic Disorders
Official title: Dietary Intervention for Psychotic Disorders: a Pilot Intervention Study of Ketogenic Diet for Psychotic Symptoms - PsyDiet Pilot Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Psychosis; Acute
Psychosis
Psychotic Disorders
Schizophrenia
Keywords: Ketogenic diet
Intervention
Ketosis
Feasibility
Psychosis
Psychotic symptoms
Schizophrenia
Dietary intervention
Lead sponsor: Kuopio University Hospital
Sponsor class: OTHER
Collaborators: name: Deakin University
First posted: 2019-03-14
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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 Niuvanniemi Hospital and 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.

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 Niuvanniemi Hospital and 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.

Eligibility 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
* changes have occurred in psychotropic medications during the last 4 weeks

Primary outcomes:
measure: The change in Positive and Negative Syndrome Scale (PANSS) total score from baseline to 6 weeks.
timeFrame: 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)
measure: Feasibility 1, defined by modified ketogenic diet related experiences, challenges and potential adverse effects during the intervention
timeFrame: 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
measure: Feasibility 2, defined by percentage of study participants who discontinue diet and percentage of participants reaching ketosis (measured by blood ketone body levels)
timeFrame: 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)
Secondary outcomes:
measure: The change in Beck Depression Inventory (BDI) score from baseline to 6 weeks.
timeFrame: Change in BDI score from baseline to 6 weeks OR if discharged earlier, from baseline to the latest study assessment time point (3 weeks)
measure: The change in Beck Anxiety Inventory (BAI) score from baseline to 6 weeks
timeFrame: Change in BAI score from baseline to 6 weeks OR if discharged earlier, from baseline to the latest study assessment time point (3 weeks)
measure: The change in Structured Clinical Interview for DSM Axis I disorders (SCID-I) diagnosis from baseline to 6 weeks
timeFrame: Change in SCID-I diagnosis from baseline to 6 weeks
measure: The change in the Global Assessment of Functioning score from baseline to 6 weeks.
timeFrame: 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)
Other outcomes:
measure: Change in Blood lipid levels
timeFrame: Change in blood lipids between baseline and 6 weeks
measure: Change in Fasting glucose levels
timeFrame: Change in blood lipids between baseline and 6 weeks
measure: Change in weight/body mass index (BMI) from baseline to 6 weeks
timeFrame: 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)
measure: Change in blood pressure (diastolic and systolic) from baseline to 6 weeks.
timeFrame: Change in blood pressure from baseline to 6 weeks OR if discharged earlier, from baseline to the latest study assessment time point (3 weeks)
Locations:
city: Kuopio
country: Finland
facility: Kuopio University Hospital, Department of Psychiatry
Study officials:
affiliation: Kuopio University Hospital
name: Anu Ruusunen, PhD
role: PRINCIPAL_INVESTIGATOR
References: