Common Noradrenergic Mechanisms in Parkinson´s Disease and L-DOPA Induced Dyskinesia

NCT02578849 | Unknown DMC

• 1 other identifier: 0602_Parkinson´s disease
• Study Type: observational
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

The aims of this proposal include tests of hypotheses of the pathogenetic mechanisms of noradrenergic neurotransmission in Parkinson's disease in vivo, using positron emission tomography of patients with early and advanced Parkinson's disease with or without 3,4 L-dihydroxyphenylalanine (L-DOPA) - induced dyskinesia or co-morbid depression, and evaluation of whether these mechanisms can be influenced therapeutically. Hypotheses:

1. 1.The investigators argue that release in human cortical and subcortical brain regions of norepinephrine (NE) derived from metabolism of exogenousL-DOPA is greater in Parkinson's disease patients with L-DOPA- induced dyskinesia than in patients without this complication. This hypothesis will be tested by measuring antagonist \[11C\]yohimbine binding to alpha-2 adrenoceptors before and after L-DOPA challenge.
2. 2.If so, it is argued that the greater rise of norepinephrine, measured as \[11C\]yohimbine displacement after L-DOPA challenge, is the result of down-regulation or loss of norepinephrine transporters. This hypothesis will be tested by measuring the binding of \[11C\]MeNER, a tracer of norepinephrine transporters.
3. 3.If so, the investigators argue that the greater decline of \[11C\]MeNER binding is significantly correlated to the symptoms of Parkinson's disease, as proof that patients with more severe loss of noradrenergic terminals exhibit more severe motor deficits.

Conditions

Parkinson´s Disease

Outcome Measures

Primary Outcomes (1)

• Noradrenaline release

  Quantification of noradrenaline release in patients with Parkinson´s disease and healthy controls after pretreatment with 150mg L-DOPA as evaluated with \[11C\]yohimbine positron. emission tomography.

  Up to 16 months

Secondary Outcomes (1)

• Noradrenaline transporters

  Up to 16 months

Study Arms (3)

PD_no_LID

Patients with Parkinson´s disease without dyskinesia

Drug: L-DOPA

PD_LID

Patients with Parkinson´s disease with L-DOPA induced dyskinesia

Drug: L-DOPA

HC

Health controls, age-mathced.

Drug: L-DOPA

Interventions

L-DOPA DRUG

Patients and healthy controls are recruited to participate in \[11C\]yohimbine scans before and after L-DOPA challenge.

Also known as: Sinemet

HC; PD_LID; PD_no_LID

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Parkinson´s disease patients with/without L-DOPA induced dyskinesia and age-matched healthy controls.

You may qualify if:

• patients with PD in the age between 50 og 80, Hoehn og Yahr stage 2-3, never L-DOPA induced dyskinesia.
• patients with PD in the age between 50 og 80 år, Hoehn og Yahr stage 2-3, with established L-DOPA induced dyskinesia.
• age matched healthy controls.

You may not qualify if:

• Psychiatric or neurological disease, not related to Parkinson´s disease.
• Cancer and malignant disease.
• Liver or kidney disease.
• Alcohol or substance abuse.
• Cardiac disease.
• Treatment with antipsychotics or antiepileptics or other medications that affect the noradrenergic system. Medicines to treat Parkinson´s disease are allowed.
• Patients treated with deep brain stimulation.

Sponsors & Collaborators

• Aarhus University Hospital: lead
• University of Copenhagen: collaborator

Study Sites (1)

Department of Nuclear Medicine and PET-Centre, Aarhus University Hospital

Aarhus C, Denmark, 8000,, Denmark

RECRUITING

Related Publications (10)

• Sara SJ. The locus coeruleus and noradrenergic modulation of cognition. Nat Rev Neurosci. 2009 Mar;10(3):211-23. doi: 10.1038/nrn2573. Epub 2009 Feb 4.

  PMID: 19190638 RESULT

• Rascol O, Schelosky L. 123I-metaiodobenzylguanidine scintigraphy in Parkinson's disease and related disorders. Mov Disord. 2009;24 Suppl 2:S732-41. doi: 10.1002/mds.22499.

  PMID: 19877202 RESULT

• Hawkes CH, Del Tredici K, Braak H. A timeline for Parkinson's disease. Parkinsonism Relat Disord. 2010 Feb;16(2):79-84. doi: 10.1016/j.parkreldis.2009.08.007. Epub 2009 Oct 28.

  PMID: 19846332 RESULT

• Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson's disease. Neurobiol Aging. 2003 Mar-Apr;24(2):197-211. doi: 10.1016/s0197-4580(02)00065-9.

  PMID: 12498954 RESULT

• Buck K, Ferger B. Comparison of intrastriatal administration of noradrenaline and l-DOPA on dyskinetic movements: a bilateral reverse in vivo microdialysis study in 6-hydroxydopamine-lesioned rats. Neuroscience. 2009 Mar 3;159(1):16-20. doi: 10.1016/j.neuroscience.2008.12.026. Epub 2008 Dec 24.

  PMID: 19146929 RESULT

• Ahlskog JE, Muenter MD. Frequency of levodopa-related dyskinesias and motor fluctuations as estimated from the cumulative literature. Mov Disord. 2001 May;16(3):448-58. doi: 10.1002/mds.1090.

  PMID: 11391738 RESULT

• Fox SH, Lang AE, Brotchie JM. Translation of nondopaminergic treatments for levodopa-induced dyskinesia from MPTP-lesioned nonhuman primates to phase IIa clinical studies: keys to success and roads to failure. Mov Disord. 2006 Oct;21(10):1578-94. doi: 10.1002/mds.20936.

  PMID: 16874752 RESULT

• Schapira AH, Olanow CW. Drug selection and timing of initiation of treatment in early Parkinson's disease. Ann Neurol. 2008 Dec;64 Suppl 2:S47-55. doi: 10.1002/ana.21460.

  PMID: 19127579 RESULT

• Jakobsen S, Pedersen K, Smith DF, Jensen SB, Munk OL, Cumming P. Detection of alpha2-adrenergic receptors in brain of living pig with 11C-yohimbine. J Nucl Med. 2006 Dec;47(12):2008-15.

  PMID: 17138744 RESULT

• Landau AM, Dyve S, Jakobsen S, Alstrup AK, Gjedde A, Doudet DJ. Acute Vagal Nerve Stimulation Lowers alpha2 Adrenoceptor Availability: Possible Mechanism of Therapeutic Action. Brain Stimul. 2015 Jul-Aug;8(4):702-7. doi: 10.1016/j.brs.2015.02.003. Epub 2015 Feb 13.

  PMID: 25758422 RESULT

MeSH Terms

Conditions

Parkinson Disease

Interventions

Levodopa; carbidopa, levodopa drug combination

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Dihydroxyphenylalanine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Phenylalanine; Amino Acids, Aromatic; Amino Acids, Cyclic; Amino Acids; Amino Acids, Peptides, and Proteins; Tyrosine

Central Study Contacts

Adjmal Nahimi, MD

CONTACT

+4553639856; adjmalnahimi@gmail.com

Michele Gammeltoft, Secretary

CONTACT

78461381; michgamm@rm.dk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PhD

Study Record Dates

• First Submitted: September 30, 2015
• First Posted: October 19, 2015
• Study Start: January 1, 2012
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: October 19, 2015

Record last verified: 2015-10

Locations

DK (1)