Brain Insulin Resistance and Motivation in Mood Disorders
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Effort-Expenditure for Rewards Task (EEfRT)
研究概览
简要总结
The overarching aim of the study is to determine the role of insulin signaling on the neurobiological substrates subserving anhedonia within individuals with mood disorders (i.e., Bipolar Disorder (BD) and Major Depressive Disorder (MDD)).
Specific aims include:
- Molecular: Assessment of components of the insulin cascade, as well as of anhedonia and reward-related processes, using a proteomics and gene expression approach;
- Physiology: Measurement of peripheral sensitivity to insulin and metabolic correlates, including body mass index and dyslipidemia;
- Neural Circuits: Evaluation of the insulin sensitivity of prefrontal (e.g. prefrontal cortex) and striatal (e.g. nucleus accumbens, ventral tegmental area) networks in the resting-state and during an effort-based decision making test, using acutely administered intranasal insulin and functional magnetic resonance imaging (fMRI);
- Behavioral: Measurement of willingness to make effort for rewards, as well as of other components of reward response and anhedonia, using validated behavioral tasks and clinical scales (e.g. Snaith-Hamilton Pleasure Scale - SHPS).
This initiative represents a proof-of-concept study that insulin is important to anhedonia, neurocognitive functioning, and behavioural deficits in MDD, representing a novel and safe therapeutic avenue.
详细描述
Seventy-five adults between the ages of 18 to 50 years with DSM-5 defined MDD or BDI/II, in a depressive episode will be enrolled, in addition to seventy-five age- and sex-matched healthy controls. Enrollment into the study is voluntary. Eligible participants will provide written informed consent. Participants will be enrolled from the outpatient Mood Disorders Psychopharmacology Unit (MDPU), University Health Network (UHN), University of Toronto.
The MDPU case report form will gather information on the participant's course of illness variables. Conventional pharmacological treatments for MDD and BD will be permitted.
Participants will be excluded if they are receiving insulin and/or oral hypoglycemiants; have been diagnosed with possible or probable Alzheimer's Disease, Mild Cognitive Impairment, or any other dementia; have a history of neurological disorder, or evidence of neurologic or other physical illness that could produce cognitive deterioration; have substance use disorder within 3 months before screening or a positive baseline toxicology screen; have a clinically unstable general medical illness; are pregnant or breastfeeding; have MRI contraindications.
The ongoing provision of care is not contingent on enrollment and/or completion of the study protocol. Furthermore, there will be ongoing communication with the participant's primary care provider in regards to their participation in this study.
This is a randomized double-blind, placebo-controlled, cross-over study. The initial visit entails the provision of detailed study information to the patient and obtainment of written informed consent from the participant. The participant will then meet a research team member at a later date for a screening visit. This study requires a total of 3 visits: one screening visit and two fMRI scan visits.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 60 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Insulin
Intranasal insulin will be made prepared from Humulin® R [insulin injection, human biosynthetic (rDNA Origin) REGULAR; 10 mL/vial, manufactured by Eli Lilly]. Each mL contains: 100 units of insulin injection, human biosynthetic (rDNA Origin) REGULAR. Nonmedicinal ingredients contain: glycerol, hydrochloric acid, m-cresol, sodium hydroxide and water for injection.
Unopened vials should be stored under refrigeration between 2°C and 8°C (36°F to 46°F) until the expiration date; do not freeze; keep away from heat and sunlight. Once punctured (in use), Humulin vials should be stored at room temperature <25°C (<77°F) and discarded after 28 days.
To obtain a dose Humulin R 160 U / placebo
- 16 sprays (0.1 mL/spray) are to be given per dose
- This works out to 16 sprays split between each nostril such that each nostril receives 8 sprays.
- The sprays will be administered between alternating nostrils
干预措施: Humulin R (Drug)
Sterile Diluent
Intranasal placebo will be prepared from Eli Lilly's sterile diluent used with Humulin® R (10 mL/vial, manufactured by Eli Lilly). Nonmedicinal ingredients contain: dibasic sodium phosphate, glycerin, liquefied phenol, metacresol, hydrochloric acid, sodium hydroxide and water for injection.
Unused sterile diluent should be kept at controlled room temperature until the expiration date. The USP defines controlled room temperature as (20° to 25°C [68° to 77°F]), with excursions permitted (15° to 30°C [59° to 86°F]). Once in-use, the sterile diluent vial should be used within 28 days.
Participants will follow the same dosage, frequency, and administration as Humulin:
- 16 sprays (0.1 mL/spray) are to be given per dose
- This works out to 16 sprays split between each nostril such that each nostril receives 8 sprays.
- The sprays will be administered between alternating nostrils
干预措施: Diluent (Drug)
结局指标
主要结局
Effort-Expenditure for Rewards Task (EEfRT)
时间窗: 2 weeks
Score from the end of each treatment phase.
次要结局
- Young Mania Rating Scale (YMRS)(2 weeks)
- Montgomery-Asberg Depression Scale (MADRS)(2 weeks)
- Snaith-Hamilton Pleasure Scale (SHAPS)(2 weeks)
- Perceived Deficits Questionnaire-Depression (PDQ-D)(2 weeks)
- Sheehan Disability Scale (SDS)(2 weeks)
- The DeJong Gierveld Loneliness Scale(2 weeks)
- International Physical Activity Questionnaire (IPAQ)(2 weeks)
- Pittsburgh Sleep Quality Index (PSQI)(2 weeks)
- Social and Occupational Functioning Assessment Scale (SOFAS)(2 weeks)
- Digit Symbol Substitution Test (DSST)(2 weeks)
- Rey Auditory Verbal Learning Test (RAVLT)(2 weeks)
- Trail Making Test A/B (TMT A/B)(2 weeks)
研究者
Rodrigo Mansur
Psychiatrist, Assistant Professor of Psychiatry at the University of Toronto
University Health Network, Toronto