Pilot Trial of Transnasal Nicotine in Parkinson Disease
Pilot Trial of Transnasal Nicotine in Parkinson Disease
The widely observed inverse relationship between smoking and Parkinson's Disease (PD) and the
 results of numerous preclinical studies indicating neuroprotective effects of nicotine,
 suggest a possible novel intervention in PD. 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. The investigators believe that pulsatile stimulation of the
 central nicotinic receptors (achievable via nasal spray) would affect the dynamic of the
 nicotinic receptors much more desirably and similar to smoking compared to continuous
 nicotine administration via patch, which might result in continuous nicotinic receptor
 desensitization. Thus, this pilot trial seeks to evaluate the efficacy of nicotine nasal
 spray (Nicotrol NS®) in symptomatology of PD. For this purpose, a total of 6 non-smoking
 patients at intermediate disease stages (2-3 of Hoehn and Yahr scale) and receiving
 conventional therapy for PD will be recruited at the "Instituto Nacional de Neurología y
 Neurocirugía, (Manuel Velasco Suárez)" in Mexico City. Nicotrol NS® in incremental dosing (up
 to 10 mg/day) regimens will be added to the current medications to each patient during the
 first week. This will be maintained for up to 1 month. Motor and non-motor aspects of PD will
 be evaluated. The investigators expect significant improvement of motor and non-motor
 symptoms in all patients receiving Nicotrol NS® during therapy and a reversal during
 withdrawal.
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?
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