Pilot Trial of Transnasal Nicotine in Parkinson Disease
Ключови думи
Резюме
Описание
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?
Дати
| Последна проверка: | 10/31/2019 |
| Първо изпратено: | 02/25/2019 |
| Очаквано записване подадено: | 03/03/2019 |
| Първо публикувано: | 03/05/2019 |
| Изпратена последна актуализация: | 11/03/2019 |
| Последна актуализация публикувана: | 11/05/2019 |
| Действителна начална дата на проучването: | 03/03/2019 |
| Приблизителна дата на първично завършване: | 11/01/2019 |
| Очаквана дата на завършване на проучването: | 11/01/2019 |
Състояние или заболяване
Интервенция / лечение
Drug: Nicotine Nasal Spray 10 MG/ML
Фаза
Групи за ръце
| Arm | Интервенция / лечение |
|---|---|
| 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. |
Критерии за допустимост
| Възрасти, отговарящи на условията за проучване | 60 Years Да се 60 Years |
| Полове, допустими за проучване | All |
| Приема здрави доброволци | Да |
| Критерии | 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 |
Резултат
Първични изходни мерки
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]
