Parkinson DiseasePhase 2NCT03865121
Pilot Trial of Transnasal Nicotine in Parkinson Disease
A Phase 2 study testing Nicotine Nasal Spray 10 MG/ML (0.5 MG/SPRAY) in people with Parkinson Disease, run by El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez at 1 site in Mexico.
Trial 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. Read more about this study
- Who is it for?
- Ages 60 years and older
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- Nicotine Nasal Spray 10 MG/ML (0.5 MG/SPRAY)
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteMexico
- Study dates
- 4 Mar 2019to 2 Nov 2019
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 60 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
Who cannot join
- Unable to complete follow-up protocol
- Drug adverse reaction
- Death
Trial locations and contacts
1 site in 1 country.
Mexico1 site
Instituto Nacional de Neurología y Neurocirugía MVS
Mexico City, 14269
About this study
Official title: 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.
Read the 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?
- Conditions
- Parkinson Disease
- Being tested
- Nicotine Nasal Spray 10 MG/ML (0.5 MG/SPRAY)
- Keywords
- Parkinson Disease, Nicotine, Transnasal
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nicotine Nasal Spray 10 MG/ML (0.5 MG/SPRAY)Drug
Also called Nicotine Nasal 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.
| Study group | Role | What they receive |
|---|---|---|
| Nicotine Nasal Spray 10 MG/ML | Experimental | 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. Receives: Drug: Nicotine Nasal Spray 10 MG/ML (0.5 MG/SPRAY) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from in motor dysfunction as assessed by MDS-UPDRS (Movement Disorder Society Unified Parkinson Disease subscale 3, range 0 best -56 worse ).
Change from baseline in motor dysfunction as assessed by MDS-UPDRS (Movement Disorder Society Unified Parkinson Disease subscale 3, range 0 best -56 worse ).
Measured: 1 month
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Mar 2019
- Study start4 Mar 2019
- Primary completion2 Nov 2019
- Study completion2 Nov 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Uncontrolled Pilot Trial
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez
- Sponsor type
- University, hospital or other
- Collaborators
- Howard University
- Responsible party
- Principal investigator, Leo Bayliss-Amaya, El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez
- Investigators
- Mayela Rodríguez Violante, MSc., Principal investigator, El Instituto Nacional de Neurologia Manuel Velasco Suarez
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03865121
- Sponsor's protocol ID
- INNNMVS
- Status last verified
- Nov 2019
- First submitted
- 26 Feb 2019
- Last updated
- 6 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Quik M. Smoking, nicotine and Parkinson's disease. Trends Neurosci. 2004 Sep;27(9):561-8. doi: 10.1016/j.tins.2004.06.008.
PubMed 15331239Tizabi Y, Getachew B. Nicotinic Receptor Intervention in Parkinson's Disease: Future Directions. Clin Pharmacol Transl Med. 2017;1(1):14-19. Epub 2017 Mar 6.
PubMed 29863173Tizabi Y, Getachew B, Rezvani AH, Hauser SR, Overstreet DH. Antidepressant-like effects of nicotine and reduced nicotinic receptor binding in the Fawn-Hooded rat, an animal model of co-morbid depression and alcoholism. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Apr 30;33(3):398-402. doi: 10.1016/j.pnpbp.2008.09.010. Epub 2008 Sep 19.
PubMed 18835320Villafane G, Cesaro P, Rialland A, Baloul S, Azimi S, Bourdet C, Le Houezec J, Macquin-Mavier I, Maison P. Chronic high dose transdermal nicotine in Parkinson's disease: an open trial. Eur J Neurol. 2007 Dec;14(12):1313-6. doi: 10.1111/j.1468-1331.2007.01949.x. Epub 2007 Oct 17.
PubMed 17941858Villafane G, Thiriez C, Audureau E, Straczek C, Kerschen P, Cormier-Dequaire F, Van Der Gucht A, Gurruchaga JM, Quere-Carne M, Evangelista E, Paul M, Defer G, Damier P, Remy P, Itti E, Fenelon G. High-dose transdermal nicotine in Parkinson's disease patients: a randomized, open-label, blinded-endpoint evaluation phase 2 study. Eur J Neurol. 2018 Jan;25(1):120-127. doi: 10.1111/ene.13474. Epub 2017 Oct 23.
PubMed 28960663
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Uncontrolled Pilot Trial of Transnasal Nicotine in Parkinson Disease
- ClinicalTrials.gov ID
- NCT03865121
- Acronym / sponsor ID
- INNNMVS
- Conditions
- Parkinson Disease
- Keywords
- Parkinson Disease, Nicotine, Transnasal
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco SuarezUniversity, hospital or other
- Collaborators
- Howard University
- Study start
- 4 Mar 2019 (actual)
- Primary completion
- 2 Nov 2019 (actual)
- Study completion
- 2 Nov 2019 (actual)
- First posted
- 6 Mar 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Uncontrolled Pilot Trial
| Arm | Type | Receives |
|---|---|---|
| Nicotine Nasal Spray 10 MG/ML | Experimental | 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. |
Who may qualify
- Ages
- 60 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 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
Key exclusion criteria (3 listed)
- Unable to complete follow-up protocol
- Drug adverse reaction
- Death
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nicotine Nasal Spray 10 MG/ML (0.5 MG/SPRAY)Also: Nicotine Nasal SprayPatients 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 |
Primary outcome
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 ).
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2019.
- Results publication: PubMed 15331239Quik M. Smoking, nicotine and Parkinson's disease. Trends Neurosci. 2004 Sep;27(9):561-8. doi: 10.1016/j.tins.2004.06.008.
- Results publication: PubMed 29863173Tizabi Y, Getachew B. Nicotinic Receptor Intervention in Parkinson's Disease: Future Directions. Clin Pharmacol Transl Med. 2017;1(1):14-19. Epub 2017 Mar 6.
- Results publication: PubMed 18835320Tizabi Y, Getachew B, Rezvani AH, Hauser SR, Overstreet DH. Antidepressant-like effects of nicotine and reduced nicotinic receptor binding in the Fawn-Hooded rat, an animal model of co-morbid depression and alcoholism. Prog Neuropsychopharmacol Biol Psychiatry. 2009 Apr 30;33(3):398-402. doi: 10.1016/j.pnpbp.2008.09.010. Epub 2008 Sep 19.
- Results publication: PubMed 17941858Villafane G, Cesaro P, Rialland A, Baloul S, Azimi S, Bourdet C, Le Houezec J, Macquin-Mavier I, Maison P. Chronic high dose transdermal nicotine in Parkinson's disease: an open trial. Eur J Neurol. 2007 Dec;14(12):1313-6. doi: 10.1111/j.1468-1331.2007.01949.x. Epub 2007 Oct 17.
- Results publication: PubMed 28960663Villafane G, Thiriez C, Audureau E, Straczek C, Kerschen P, Cormier-Dequaire F, Van Der Gucht A, Gurruchaga JM, Quere-Carne M, Evangelista E, Paul M, Defer G, Damier P, Remy P, Itti E, Fenelon G. High-dose transdermal nicotine in Parkinson's disease patients: a randomized, open-label, blinded-endpoint evaluation phase 2 study. Eur J Neurol. 2018 Jan;25(1):120-127. doi: 10.1111/ene.13474. Epub 2017 Oct 23.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mayela Rodríguez Violante, MSc. principal investigator
El Instituto Nacional de Neurologia Manuel Velasco Suarez
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nicotine Nasal Spray 10 MG/ML (0.5 MG/SPRAY) in people with Parkinson Disease, run by El Instituto Nacional de Neurologia y Neurocirugia Manuel Velasco Suarez at 1 site in Mexico.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mexico. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03865121, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2019.