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Pilot Trial of Transnasal Nicotine in Parkinson Disease

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ClinicalTrials.gov Identifier: NCT03865121
Recruitment Status : Not yet recruiting
First Posted : March 6, 2019
Last Update Posted : March 6, 2019
Sponsor:
Collaborator:
Howard University
Information provided by (Responsible Party):
Leo Bayliss-Amaya, El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Parkinson Disease Drug: Nicotine Nasal Spray 10 MG/ML (0.5 MG/SPRAY) Phase 2

Detailed Description:

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?


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Intervention Model: Single Group Assignment
Intervention Model Description: Uncontrolled Pilot Trial
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Uncontrolled Pilot Trial of Transnasal Nicotine in Parkinson Disease
Estimated Study Start Date : March 4, 2019
Estimated Primary Completion Date : September 2, 2019
Estimated Study Completion Date : December 20, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 (0.5 MG/SPRAY)
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.
Other Name: Nicotine Nasal Spray




Primary Outcome Measures :
  1. To evaluate the Efficacy of treatment during one month with nicotine nasal spray (Nicotrol NS®) in motor aspects of PD as assessed by MDS-UPDRS (Movement Disorder Society Unified Parkinson Disease) scores [ Time Frame: 1 month ]
    If drug is effective MDS-UPDRS (Movement Disorder Society Unified Parkinson Disease) scores will decrease



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Ages Eligible for Study:   60 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03865121


Contacts
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Contact: Leo Bayliss Amaya, MD +52 56063822 ext 1037 leobayliss@gmail.com

Sponsors and Collaborators
El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez
Howard University
Investigators
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Principal Investigator: Mayela Rodríguez Violante, MSc. El Instituto Nacional de Neurologia Manuel Velasco Suarez

Publications of Results:
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Responsible Party: Leo Bayliss-Amaya, Attending Neurologist, El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez
ClinicalTrials.gov Identifier: NCT03865121     History of Changes
Other Study ID Numbers: INNNMVS
First Posted: March 6, 2019    Key Record Dates
Last Update Posted: March 6, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes

Keywords provided by Leo Bayliss-Amaya, El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez:
Parkinson Disease
Nicotine
Transnasal

Additional relevant MeSH terms:
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Parkinson Disease
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Nicotine
Ganglionic Stimulants
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Nicotinic Agonists
Cholinergic Agonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action