Gastrointestinal Dopamine Decarboxylase and Levodopa Pharmacokinetics
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- levodopa pharmacodynamics
研究概览
简要总结
The main treatment for Parkinson's disease is a medication called levodopa. Levodopa has to be absorbed from the gut and travel to the brain to work, but a naturally occurring enzyme in the lining of the stomach, called dopamine decarboxylase (AADC), can break some of it down before it ever reaches the brain. We do not yet know whether people whose stomachs have more of this enzyme absorb less of their levodopa dose, have worsened gastrointestinal (GI) symptoms associated with levodopa intake, and whether that affects how well the medication controls their movement symptoms. This research may help doctors understand why levodopa works better in some people with Parkinson's disease than others, which could help improve treatment in future.
详细描述
Patients will be asked to fast overnight prior to the study visit, including holding any doses of dopamine replacement therapy that they may be prescribed, including levodopa or equivalents, and any promotility agents, including cholinesterase inhibitors or peripherally-restricted dopamine antagonists (ie. Domperidone), that may impact gastric transit.
At the start of the study visit, patients will undergo a neurological exam by a study investigator blinded to which study group the patient belongs. Exams will be performed according to the Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Part III, a validated clinical score of motor impairment in Parkinson's disease (PD). They will also undergo a baseline blood draw (5.5 mLs) through an indwelling venous cannula in the antecubital vein. Immediately afterwards, a single oral dose of levodopa (100 mg) obtained through the BIDMC research pharmacy with a standard volume of water (100 mL). Repeat blood samples will be collected immediately after oral levodopa ingestion (T=0) and then repeated every ½ hour until T=4 hours for a total of 10 draws, including the baseline. The initial placement of indwelling venous cannula will mitigate the necessity for repeated venipuncture during the study visit. At each ½ hour interval, additionally, patients will undergo repeat MDS-UPDRS-III assessments. After the 4-hour study concludes, the patient will be allowed to consume any food they would like and can resume home medications as previously prescribed clinically. Blood samples will be centrifuged to separate plasma and immediately frozen at -80oC until analysis by an investigator blinded to which study group the patient belongs.
Separately, patients' prior clinically-obtained gastric biopsy blocks will be requested from BIDMC pathology (as otherwise discarded specimen) and stained for presence of AADC. This will not require any further time or visits from the patient themselves.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- None
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Parkinson's disease
- •Gastric biopsies previously obtained during clinically-indicated EGD procedure
- •Taking dopamine replacement therapy currently
排除标准
- •No history of Parkinson's disease
研究组 & 干预措施
Elevated AADC
Participants will be administered a single dose of levodopa at the start of the study period
干预措施: Levodopa (L-dopa) (Drug)
Non-elevated AADC
Participants will be administered a single dose of levodopa at the start of the study period
干预措施: Levodopa (L-dopa) (Drug)
结局指标
主要结局
levodopa pharmacodynamics
时间窗: 0-4 hours after oral levodopa ingestion.
Peripheral levodopa levels will be assessed via blood draw to determine time (in minutes) to reach maximum concentration in the blood. Lower Tmax indicates quicker bioavailability.
次要结局
- The Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score(0-4 hours after oral levodopa ingestion)
研究者
Trisha Pasricha
Assistant Professor of Medicine
Beth Israel Deaconess Medical Center
