Dopaminergic Therapy for Inflammation-Related Anhedonia in Depression
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 19
- 试验地点
- 1
- 主要终点
- Targeted Ventral Striatum to Ventromedial Prefrontal Cortex (VS-vmPFC) Connectivity
研究概览
简要总结
The purpose of this 6-week, double-blind, placebo-controlled, crossover study is to explore new treatment options for people with depression who have high inflammation and anhedonia. Thirty-five male and female participants with depression, between the ages of 25-55 years of age, will be randomized to two study tracks (A and B) to receive both placebo and three doses of L-DOPA, given in different orders. Increases or decreases in each dose will occur gradually over 6 weeks of the study. Participants will complete lab tests, medical and psychiatric assessments, neurocognitive testing and functional MRI (fMRI) scans as part of the study. The total length of participation is about 2 months.
详细描述
Depression is a widespread disorder (lifetime prevalence >20%). Current antidepressant medications are effective for many patients; however, more than 30% fail to respond. Of the patients that do respond to treatment, some continue to suffer with primary symptoms of depression like an inability to experience pleasure, called anhedonia. In this regard, one biological pathway that may contribute to symptoms of depression and particularly anhedonia is inflammation.
The purpose of this 6-week, double-blind, placebo-controlled, crossover study is to explore new treatment options for people with depression who have high inflammation and anhedonia. Despite evidence of low dopamine function in patients with depression, the ability of existing dopaminergic therapies, like L-DOPA, to affect brain circuits in depression has yet to be explored. This study will help determine the best dose of an FDA-approved medication, Sinemet (L-DOPA) that might be used in the future to treat sub-groups of depressed individuals.
Forty male and female participants with depression, between the ages of 25-55 years of age, will be randomized to two study tracks (A and B) to receive both placebo and three doses of L-DOPA, given in different orders. Increases or decreases in each dose will occur gradually over 6 weeks of the study. Participants will complete lab tests, medical and psychiatric assessments, neurocognitive testing and functional MRI (fMRI) scans as part of the study. The total length of participation is about 2 months.
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
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 25 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •willing and able to give written informed consent;
- •men or women, 25-55 years of age
- •a primary diagnosis of DSM-V MD, current, as diagnosed by the SCID-I;
- •score >10 on the Patient Health Questionnaire [PHQ]-9
- •off all antidepressant or other psychotropic therapy (e.g. mood stabilizers, antipsychotics, anxiolytics, and sedative hypnotics) for at least 4 weeks prior to baseline visit (8 weeks for fluoxetine)
- •CRP ≥2 mg/L
- •Score >/=2 on the anhedonia question of Patient Health Questionnaire [PHQ]-9
排除标准
- •history or evidence (clinical or laboratory) of an autoimmune disorder ;
- •history or evidence (clinical or laboratory) of hepatitis B or C infection or human immunodeficiency virus infection; - history of any type of cancer requiring treatment with more than minor surgery;
- •unstable cardiovascular, endocrinologic, hematologic, hepatic, renal, or neurologic disease (as determined by physical examination, EKG and laboratory testing);
- •history of any (non-mood-related) psychotic disorder; active psychotic symptoms of any type; history or current bipolar disorder; history or current gambling disorder; substance abuse/dependence within 6 months of study entry (as determined by SCID);
- •active suicidal plan as determined by a score >3 on item #3 on the HAM-D; g. an active eating disorder (except for patients with binge eating disorder in whom binging is clearly associated with worsening of mood symptoms) ;
- •a history of a cognitive disorder
- •pregnancy or lactation;
- •chronic use of non-steroidal anti-inflammatory agents (NSAIDS) (excluding 81mg of aspirin), glucocorticoid containing medications or statins;
- •use of NSAIDS, glucocorticoids, or statins at any time during the study;
- •urine toxicology screen is positive for drugs of abuse,
- •any contraindication for MRI scanning; n. intolerance, sensitivity or contraindication to carbidopa-levodopa (including history of narrow-angle glaucoma, melanoma, gastric and/or duodenal ulcers, bleeding disorders, or frequent migraines).
研究组 & 干预措施
Carbidopa Levodopa followed by Placebo
Participants will receive first Carbidopa Levodopa at doses ranging from 150 to 450 mg administered at a ratio of 1 mg carbidopa for every 4 mg L-DOPA with a starting dose of 150 mg/day with dose escalation 150 mg/day per week to a final dose of 450 mg/day; and then placebo.
干预措施: Carbidopa Levodopa (Drug)
Carbidopa Levodopa followed by Placebo
Participants will receive first Carbidopa Levodopa at doses ranging from 150 to 450 mg administered at a ratio of 1 mg carbidopa for every 4 mg L-DOPA with a starting dose of 150 mg/day with dose escalation 150 mg/day per week to a final dose of 450 mg/day; and then placebo.
干预措施: Placebo (Drug)
Placebo followed by Carbidopa Levodopa
Participants will receive first placebo, and then Carbidopa Levodopa (L-DOPA) at doses ranging from 150 to 450 mg administered at a ratio of 1 mg carbidopa for every 4 mg L-DOPA with a starting dose of 150 mg/day with dose escalation 150 mg/day per week to a final dose of 450 mg/day.
干预措施: Carbidopa Levodopa (Drug)
Placebo followed by Carbidopa Levodopa
Participants will receive first placebo, and then Carbidopa Levodopa (L-DOPA) at doses ranging from 150 to 450 mg administered at a ratio of 1 mg carbidopa for every 4 mg L-DOPA with a starting dose of 150 mg/day with dose escalation 150 mg/day per week to a final dose of 450 mg/day.
干预措施: Placebo (Drug)
结局指标
主要结局
Targeted Ventral Striatum to Ventromedial Prefrontal Cortex (VS-vmPFC) Connectivity
时间窗: Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day)
Patients will undergo resting-state and task-based functional magnetic resonance imaging (fMRI) to calculate functional connectivity (FC) between the ventral striatum (VS) and ventromedial prefrontal cortex (vmPFC). FC is measured as continuous Z scores reflecting the correlation of activity between the brain regions using Fisher's Z transformation {Z(R)=0.5ln\[(1+R)/(1-R)\]}. This is a standard method for calculating fMRI FC whereby higher FC Z scores reflect stronger connectivity.
次要结局
- Effort-Expenditure for Rewards Task (EEfRT)(Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day))
- Inventory of Depressive Symptomatology- Self-Report (IDS-SR) Anhedonia Scale(Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day))
- Hedonic Capacity as Measured by the Snaith Hamilton Pleasure Clinician Scale (SHAPS-C )(Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day))
- Motivation and Pleasure-Self-Report (MAP-SR)(Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day))
- Hamilton Depression Rating Scale (HAM-D) Anhedonia and Motivation Item(Baseline, 1-week of placebo, and 1-week at each dose of L-DOPA (150 mg/day, 300 mg/day and 450 mg/day))
研究者
Jennifer Felger
Associate Professor
Emory University