Pilot Trial of Transnasal Nicotine in Parkinson Disease
關鍵詞
抽象
描述
Parkinson's disease (PD), the second most common progressive neurodegenerative disorder, is associated with loss of dopaminergic neurons in the substantia nigra pars compacta that leads to striatal dopamine deficiency. This dopaminergic loss results in motor deficits characterized by: akinesia, rigidity, resting tremor and postural instability as well as non-motor symptoms that might also involve other neurotransmitter systems. The non-motor symptoms may include: cognitive deficits (e.g., mild to severe memory impairment), emotional changes (e.g., depression, apathy and anxiety), sleep perturbations (e.g., insomnia/hypersomnia), autonomic dysfunction (e.g., bladder disturbances, orthostatic hypotension, sweating), sensory symptoms (e.g., pain, visual and olfactory deficits) and gastrointestinal symptoms (e.g., constipation, nausea).
Parkinson's disease current treatment of choice is replacement of dopamine with its precursor Levodopa (L-Dopa), which unfortunately loses its effectiveness and can cause dyskinesia following prolonged usage. This fact motivates the search for new pharmacological strategies to better control the symptoms and/or progression of the disease.
The inverse relationship between smoking and PD has been confirmed by a number of epidemiological studies. Moreover, numerous preclinical studies indicate neuroprotective effects of nicotine. Thus, nicotine may offer a novel intervention in PD. Although use of nicotine patch has been suggested in some neurodegenerative disorders, including PD, the investigators believe that the key for success with nicotinic intervention, particularly in PD, relies on mode of nicotine administration. In our opinion, an optimal nicotinic therapy in PD would consist of pulsatile nicotine delivery (e.g. via nasal spray) similar to pulsatile nicotine obtained via smoking. Pulsatile stimulation of the central nicotinic receptors (achievable via nasal spray) would affect the dynamic of the nicotinic receptors much more desirably than continuous nicotine administration via patch, which can result in continuous nicotinic receptor desensitization. The investigators also believe that nicotine delivered via nasal spray, in addition to its potential usefulness for improving motor dysfunctions, may also be helpful in non-motor symptoms (e.g. cognitive decline and depression) that are commonly associated with neurological disorders such as PD.
Thus, this pilot clinical trial seeks to evaluate the efficacy of treatment during one month with nicotine nasal spray (Nicotrol NS®) in motor and non-motor aspects of PD.
Hypothesis: Scores of the Movement Disorders Society Unified Parkinson Disease Rating Scale (MDS-UPDRS) for motor and non-motor symptomatology will decrease after 1 month of treatment with nicotine nasal spray (Nicotrol) in patients with PD (stages 2-3 of Hoehn & Yahr).
Research question: Can controlled doses of nicotine administered via nasal spray decrease the severity of PD (stages 2-3 of Hoehn & Yahr) using MDS-UPDRS scores?
日期
| 最後驗證: | 10/31/2019 |
| 首次提交: | 02/25/2019 |
| 提交的預估入學人數: | 03/03/2019 |
| 首次發布: | 03/05/2019 |
| 上次提交的更新: | 11/03/2019 |
| 最近更新發布: | 11/05/2019 |
| 實際學習開始日期: | 03/03/2019 |
| 預計主要完成日期: | 11/01/2019 |
| 預計完成日期: | 11/01/2019 |
狀況或疾病
干預/治療
Drug: Nicotine Nasal Spray 10 MG/ML
相
手臂組
| 臂 | 干預/治療 |
|---|---|
| Experimental: Nicotine Nasal Spray 10 MG/ML Patients will receive incremental doses of Nicotine Nasal Spray 10 MG/ML (0.5 MG/SPRAY) starting with 3 bilateral puffs per day (3 mg total) for 3 days, followed by 5 bilateral puffs per day (5 mg) for 3 days, followed by 8 bilateral puffs per day (8 mg) for 4 days, followed by 10 bilateral puffs per day (10 mg) for 10 days. | Drug: Nicotine Nasal Spray 10 MG/ML Patients will receive incremental doses of Nicotine Nasal Spray 10 MG/ML (0.5 MG/SPRAY) starting with 3 bilateral puffs per day (3 mg total) for 3 days, followed by 5 bilateral puffs per day (5 mg) for 3 days, followed by 8 bilateral puffs per day (8 mg) for 4 days, followed by 10 bilateral puffs per day (10 mg) for 10 days. |
資格標準
| 有資格學習的年齡 | 60 Years 至 60 Years |
| 有資格學習的性別 | All |
| 接受健康志願者 | 是 |
| 標準 | Inclusion criteria: - Subjects over 60 years of age with a clinical diagnosis of Parkinson's disease - Stages of the disease 2-3 of Hoehn and Yahr - Not exposed to tobacco during any stage of their life - No history of lung diseases - No laboratory abnormalities - No history of adverse reactions to nicotine - Able to use nicotine nasal spray - Residents of Mexico City able to attend for evaluations - Under current treatment with levodopa at a stable dose - Not currently receiving a monoamine oxidase inhibitor treatment Exclusion Criteria - Unable to complete follow-up protocol - Drug adverse reaction - Death |
結果
主要結果指標
1. Change from in motor dysfunction as assessed by MDS-UPDRS (Movement Disorder Society Unified Parkinson Disease subscale 3, range 0 best -56 worse ). [1 month]
