Pilot Trial of Transnasal Nicotine in Parkinson Disease

November 4, 2019 updated by: Leo Bayliss-Amaya, El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez

Uncontrolled 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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?

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
      • Ciudad de Mexico, Mexico, 14269
        • Instituto Nacional de Neurologia Y Neurocirugia Mvs

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / 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 Names:
  • Nicotine Nasal Spray

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change from in motor dysfunction as assessed by MDS-UPDRS (Movement Disorder Society Unified Parkinson Disease subscale 3, range 0 best -56 worse ).
Time Frame: 1 month
Change from baseline in motor dysfunction as assessed by MDS-UPDRS (Movement Disorder Society Unified Parkinson Disease subscale 3, range 0 best -56 worse ).
1 month

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez

Collaborators

Howard University

Investigators

  • Principal Investigator: Mayela Rodríguez Violante, MSc., El Instituto Nacional de Neurologia Manuel Velasco Suarez

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 4, 2019

Primary Completion (Actual)

November 2, 2019

Study Completion (Actual)

November 2, 2019

Study Registration Dates

First Submitted

February 26, 2019

First Submitted That Met QC Criteria

March 4, 2019

First Posted (Actual)

March 6, 2019

Study Record Updates

Last Update Posted (Actual)

November 6, 2019

Last Update Submitted That Met QC Criteria

November 4, 2019

Last Verified

November 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • INNNMVS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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