外源性酮类药物对精神分裂症和双相情感障碍症状和体征的影响：一项三盲、随机、对照交叉先导研究的研究方案

IF 3.2 Q2 NUTRITION & DIETETICS

Current Developments in Nutrition Pub Date : 2025-06-01 DOI:10.1016/j.cdnut.2025.107480

Daphne AM Dielemans , Yagmur Yurtkap , Marieke van der Pluijm , Maarten R Soeters , Bob Oranje , Dirk JA Smit , Tim Ziermans , Mirjam J van Tricht , Sriram Muthukumar , Shalini Prasad , Romée L van der Mieden van Opmeer , Eline Dekeyster , Astrid M Kamperman , Jason RB Dyck , Bram-Sieben Rosema , Rocco Hoekstra , Ralph W Kupka , Lieuwe de Haan , Nico JM van Beveren , Karin Huizer

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引用次数: 0

摘要

炎症、氧化应激和生物能量功能障碍被认为是精神分裂症谱系障碍（ssd）和双相情感障碍（bd）的潜在机制，导致这些疾病中大部分未治疗的认知和阴性症状。酮体可以通过其对上述机制的积极作用为这些症状提供治疗选择。外源性酮类如酮酯（KEs）提供了一种无需饮食限制即可快速诱导酮症的方法，但其对SSD和BD的影响尚未研究。这项正在进行的三盲、随机对照交叉试验研究了单次摄入KE对SSD和BD体征和症状的影响。方法在阿姆斯特丹大学医学中心（UMC）接受住院治疗的24例患者（12例SSD和12例BD）将被纳入研究。患者将摄入单剂量的KE ((R)-3-羟基丁基-(R)-3-羟基丁酸deltaG酮（dGK）和等热量碳水化合物对照，两次饮料之间的洗脱期为3天。主要结果是与对照组相比，dGK摄入引起的惊吓反射脉冲前抑制的变化。次要结局包括静息状态脑电图、P3B振幅、认知表现、代谢、免疫、氧化应激和昼夜节律参数。可行性和潜在的副作用也将被评估。结果n /A（研究方案）。结论本研究将为KE治疗SSD和BD患者提供有价值的初步数据，为进一步研究KE在缓解这些疾病症状和改善功能结局方面的治疗潜力奠定基础。该试验在www.clinicaltrials.gov注册为NCT06426134。

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The Effect of Exogenous Ketones on Signs and Symptoms of Schizophrenia Spectrum and Bipolar Disorders: Study Protocol for a Triple-Blind, Randomized, Controlled Crossover Pilot Study

Background

Inflammation, oxidative stress, and bioenergetic dysfunction are proposed underlying mechanisms of schizophrenia spectrum disorders (SSDs) and bipolar disorders (BDs), contributing to the largely untreated cognitive and negative symptoms in these conditions. Ketone bodies may offer a therapeutic option for these symptoms through their positive effects on the aforementioned mechanisms. Exogenous ketones like ketone esters (KEs) provide a means to quickly induce ketosis without dietary restrictions, though their effects on SSD and BD have not yet been investigated.

Objectives

This ongoing triple-blind, randomized controlled crossover trial investigates the effects of a single ingestion of KE on signs and symptoms of SSD and BD.

Methods

A total of 24 patients (12 SSD and 12 BD) receiving inpatient care at Amsterdam University Medical Center (UMC) will be included in the study. Patients will ingest a single dose of KE ((R)-3-hydroxybutyl-(R)-3-hydroxybutyrate deltaG Ketones (dGK) and an isocaloric carbohydrate control with a washout period of 3 days between drinks. The primary outcome is the change in prepulse inhibition of the startle reflex induced by dGK ingestion compared with control. Secondary outcomes include resting-state electroencephalography, P3B amplitude, cognitive performance, and metabolic, immune, oxidative stress, and circadian rhythm parameters. Feasibility and potential side effects will also be assessed.

Results

N/A (study protocol).

Conclusions

Our current study will offer valuable preliminary data on the effects of KE in patients with SSD and BD. It can provide the foundation for future research into the therapeutic potential of KE in alleviating symptoms and improving functional outcomes in these disorders.

This trial was registered at www.clinicaltrials.gov as NCT06426134.

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