Networks Integrating Anxiety and Metabolism in Human Anorexia Nervosa, A Randomised Controlled Trial on Physiological and Psychological Responses to Caloric and Non-Caloric Meals
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Magnetic Resonance Imaging
研究概览
简要总结
Anorexia nervosa (AN) is known as the psychiatric disorder with the highest mortality rate as long-term calorie restriction causes medical complications and suicide risk. The ineffectiveness of pharmacological treatments increases interest in the etiopathogenesis of the disease. This study aims to examine the effects of caloric and non-caloric food intake on stress response, changes in brain network activity in AN patients and healthy volunteers, and examine whether these changes are related to caloric intake through neuroendocrine and psychological responses.
The study will include 30 female AN patients aged 13-18 who are newly diagnosed and have not received any treatment, and 30 healthy volunteers matched by age, sex, and education level. The patient group will be admitted to the clinic's open inpatient unit on the evening before the study to ensure they have fasted. A 12-hour fasting period starting from the day before the procedure will be mandatory.
In the morning, patients will undergo psychiatric assessments and scales. Psychometric measurements will be applied to determine the clinical characteristics of participants. Visual Analog Scale (VAS) will be applied. VAS is used to evaluate subjective states such as hunger, satiety, desire to eat, anxiety, fear of obesity, sadness, appetite, general mood, and motivation to participate in the study. Following this, the first resting-state functional magnetic resonance imaging (fMRI) scan will be performed for 8 minutes.
Subsequently, participants will be randomised with 1:1 allocation ratio to consume one of two jellies prepared by a dietitian: one containing 400 calories and the other calorie-free. Participants will not be forced to consume the food.
The ingredients and preparation methods were chosen to make the appearance and taste of the foods similar. Participants will not know which type of food (caloric/non-caloric) they are given. Participants who do not wish to consume the provided food will be excluded from the study. Participants will be told that the mixture they will be consuming will either be balanced in nutritional value and caloric, or harmless and calorie-free. They will be given fifteen minutes to consume the mixture, and the amount they consume will be recorded. Sixty minutes after the consumption of the mixture, participants will undergo a second fMRI scan to identify the neuronal network changes induced by this process. The same procedures will be applied to the healthy control group. Before and after imaging, blood samples will be collected from participants for biochemical analysis. Endocrine markers such as glucose, insulin, ghrelin, obestatin, PYY, leptin, and cortisol will be evaluated to assess hunger, satiety, and stress responses. Changes in these parameters will be used to evaluate participants' physiological responses to meals. A second meal will be offered three hours after the first meal, and the amount consumed will be recorded.
Four subgroups will be analysed in the study: AN patients who received calories, AN patients who did not receive calories, healthy controls who received calories, and healthy controls who did not receive calories. Outcome data will be collected before and after meal intake and the outcomes will be compared between the four groups.
The study aims to investigate the physiological, psychological and behavioural responses to caloric and non-caloric meals, and to compare the responses in patients and non-patients. It is hypothesized that the stress response observed in AN patients is not solely related to food intake but that the calorie content of the ingested food will cause additional activation in biologically stress-related networks, with corresponding effects on experience. The hypothesis that the differences observed between patients and controls are due to biological differences in AN patients will be tested. This study aims to shed light on the etiopathogenesis of AN and contribute to the development of new strategies for the treatment and management of AN.
详细描述
Methods
Design The study is designed as a single-center, parallel-group RCT with two study arms: (1) calory intake in meal-1 and (2) no calory intake in meal-1. Participants and healthy controls are individually randomized to either one of the two arms, both delivered at the eating disorder clinic of the Ege University Hospital, Faculty of Medicine.
Primary outcome measure is brain patterns observed with magnetic resonance imaging and secondary outcomes include endocrine markers in blood, cardiovascular responses, self-reported symptom severity, and subsequent food consumption.
The study is planned in accordance with the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) and will be analysed and reported in accordance with the recommendations in consolidated standards of reporting trials (CONSORT), with special care taken to meet extended recommendations for both trials with patient reported outcomes and non-pharmacological trials.
Protocol Design and Conduct To ensure transparency and integrity throughout the study, all changes or deviations from the protocol will be thoroughly documented and reported. Any modifications to the protocol, including changes to study objectives, design, participant population, sample size, procedures, or significant administrative aspects, will necessitate a formal protocol amendment. Similarly, any alterations that could potentially impact participant safety, benefits, or risks will be carefully evaluated and documented. Proposed amendments will be reviewed and approved by the study team and submitted for approval to the national ethical review board before implementation. Additionally, all relevant study personnel will be promptly informed of these changes to ensure compliance and consistency across the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 13 Years 至 18 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Female individuals
- •13-18 years of age
- •Currently patients at the eating disorder clinic
- •Newly diagnosed with AN according to the Diagnostic and Statistical Manual of mental disorders 5th edition (DSM-5)
- •Treatment naïve
- •Healthy control participants will be matched on age-, sex-, and education level with the AN-participants. The clinical diagnosis/diagnoses for participants will be validated/ruled out by the Structured Clinical Interview for DSM-5 (SCID-5). The presence of other
排除标准
- •will also be further explored at the clinical visit.
- •Exclusion criteria:
- •Having one or several chronic medical conditions that may interfere with or hinder participation, or affect study outcomes.
- •Use of medications that affect hormone levels or eating behaviors.
- •Having one or several severe psychiatric disorders other than AN (e.g., schizophrenia, major depressive disorder, bipolar disorder).
- •Current drug abuse, pregnancy or potential pregnancy (for AN patients these conditions are excluded as a part of routine care. For healthy controls no objective testing will be performed).
- •High risk of refeeding syndrome or severe complications related to eating disorders.
- •Inability to comply with the nutritional program of the study.
- •Allergies to foods included in the provided meal content.
- •Cognitive impairments preventing comprehension of the study or the informed consent process.
- •Contraindications for MRI (e.g., pacemaker, prosthesis, claustrophobia), and
- •Fasting blood glucose above 6.0 mmol/l on the morning of the study, as this indicates either non compliance with overnight fasting or pre-diabetes/diabetes..
- •Additional exclusion criterion for healthy controls: (1.) Having one or several eating disorders, current or past.
- •Participant inclusion in the study will be determined by a study clinician based on the outlined eligibility criteria. In cases of uncertainty, the principal investigator will make the final decision. Importantly, to maintain impartiality and avoid selective recruitment bias, enrolling clinicians will be masked to future treatment allocations, as randomization will occur at a later point in time.
研究组 & 干预措施
Meal with calories
Mixture prepared by a dietitian, containing 400 kilocalories.
干预措施: Meal with 400 kilocalories (Dietary Supplement)
Meal without calories
Mixture prepared by a dietitian, containing no calories.
干预措施: Meal without calories (Dietary Supplement)
结局指标
主要结局
Magnetic Resonance Imaging
时间窗: One hour post meal with/witout calories
Resting state Magnetic Resonance Imaging (MRI) and resting state functional Magnetic Resonance Imaging (fMRI)
次要结局
- Blood sample(One hour post meal with/witout calories)
- Meal-2 food consumption(Three hours post meal with/witout calories)
- Meal-1 food consumption(15 minutes post meal with/witout calories)
- Self-rated psychometrics(15 minutes, one hour and three hours post meal with/witout calories)
- Blood pressure(One hour post meal with/witout calories)
- pulse(One hour post meal with/witout calories)
研究者
Olof Lagerlöf
Assistant professor
Umeå University