Endogenous Opioid Activity and Affective State in Insulin Resistant Women
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 42
- 试验地点
- 1
- 主要终点
- Mu-opioid Receptor Binding Potential in Left Nucleus Accumbens, Resting State
研究概览
简要总结
Insulin resistance, a primary component of the metabolic syndrome, is an escalating phenomenon in the United States, and confers an increased risk of depression and mood disorder, particularly in women. The relationship between metabolic and mood disorders may be mediated by endogenous opioid activity in limbic brain regions. We propose to examine affective state and μ- opioid system function in insulin resistant women, and change in response to insulin sensitizing treatment, through the following specific aims and hypotheses:
Establish relationship between insulin resistance, affective state, and μ-opioid receptor function.
- Insulin resistant women will have greater μ-opioid receptor availability at baseline, and a larger response to stress challenge than non-insulin resistant women
- Insulin resistant women will have greater negative affective state at baseline, and a greater emotional response to stress challenge than non-insulin resistant women.
- Mediational analyses will reveal that the relationship between insulin resistance and negative affect is mediated by μ-opioid receptor function and neural activation in the amygdala and nucleus accumbens affect-regulating regions.
Examine effects of insulin regulation on μ-opioid receptor function and affective state.
- Improved insulin sensitivity will be accompanied by decreased μ-opioid receptor availability at baseline and a reduced response to stress challenge. Degree of change in baseline receptor availability and response to stress challenge after treatment will correlate with degree of insulin regulation.
- Improved insulin sensitivity will be associated with improved affective state at baseline, and with a reduced emotional response to stress challenge. Degree of change in affective state and emotional response to stress challenge after treatment will correlate with degree of insulin regulation.
- Mediational analyses will reveal that the change in affective state after insulin regulation is mediated by change in μ-opioid receptor function and neural activation in the amygdala and nucleus accumbens.
The expected results would suggest a role for the endogenous μ-opioid system in mediating the relationship between metabolic function and emotional processes.
详细描述
The objective of this study is to examine the role of the endogenous mu-opioid system in mediating the relationship between metabolic dysfunction and depressive symptoms in reproductive aged women.
PET image data was unable to be analyzed due to PET equipment replacement midway through study, leaving PET images collected at beginning of study incompatible with PET images collected later in study.
Due to insufficient enrollment in treatment arms, the 20 or 40 week data was unusable for analytic goals, so the study was re-framed for what could usefully be learned about baseline characteristics among the study populations and the originally planned outcome measures were amended to only to those that related to understanding the baseline population.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •18-40 years old
- •metabolically healthy or insulin resistant (insulin sensitivity > 1.89x10-4 (min-1 x µU-1 x mL-1; calculated by minimal model assessment of glucose tolerance test)
- •body mass index (BMI = weight (kg) / height2 (m2)) between 18 kg/m2 and 35 kg/m
- •Women with mild or moderate depressive symptoms not meeting the criteria for Major Depressive Disorder will be included.
排除标准
- •left handed
- •acute medical illness
- •uncorrected thyroid disease
- •diabetes (fasting glucose ≥126 mg/dL)\
- •neurological disease
- •major depression
- •substance abuse
- •MRI contraindications (claustrophobia, pacemakers, pumps, metallic agents or devices)
- •severe calorie restriction
- •intense physical exercise ≥1 hour/day
- •smoking within 6 months
- •hormonal, insulin sensitizing, or centrally acting medications within 2 months
- •pregnancy within 6 months
- •lactation
- •cardiac or pulmonary insufficiency
- •liver or renal insufficiency (>2.5 x normal transaminases levels, plasma creatinine ≥1.4 mg/dL)
- •history of lactic acidosis
- •BMI ≥35 kg/m2
- •opioid allergy
研究组 & 干预措施
Metformin
16 weeks treatment with metformin (insulin sensitizing treatment)
干预措施: Metformin (Drug)
Placebo
Placebo comparator to metformin treatment
干预措施: Placebo (Drug)
结局指标
主要结局
Mu-opioid Receptor Binding Potential in Left Nucleus Accumbens, Resting State
时间窗: Baseline, 20 weeks, 40 weeks
Mu-opioid neurotransmission in limbic brain regions at baseline and change from baseline after metformin treatment
Mu-opioid Receptor Binding Potential in Right Nucleus Accumbens, Resting State
时间窗: Baseline, 20 weeks, 40 weeks
Mu-opioid neurotransmission in limbic brain regions at baseline and change from baseline after metformin treatment
Mu-opioid Receptor Binding Potential in Left Amygdala, Resting State
时间窗: Baseline, 20 weeks, 40 weeks
Mu-opioid neurotransmission in limbic regions at baseline and change from baseline after metformin treatment
Mu-opioid Receptor Binding Potential in Right Amygdala, Resting State
时间窗: Baseline, 20 weeks, 40 weeks
Mu-opioid neurotransmission in limbic brain regions at baseline and change from baseline after metformin treatment
次要结局
- Positive and Negative Affect Schedule - Positive Affective State(Baseline)
- Positive and Negative Affect Schedule - Negative Affective State(Baseline)
- Profile of Mood States - Overall Negative Mood(Baseline)
- Beck Depression Index(Baseline)
研究者
Alison Berent-Spillson
Research Investigator
University of Michigan