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Parkinson DiseaseNCT03602924

Long-term Safety and Effectiveness of Levodopa-carbidopa Intestinal Gel Infusion

An observational study of Parkinson Disease, run by Hospital Universitari Vall d'Hebron Research Institute at 1 site in Spain.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

Levodopa-carbidopa intestinal gel (LCIG) infusion has demonstrated to improve motor fluctuations. The aim of this study is to assess the long-term safety and effectiveness of LCIG infusion in advanced Parkinson's disease (PD) patients with motor fluctuations and its effect in non-motor symptoms. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
Parkinson Disease
How many people
40 participants
Where
1 siteSpain
Study dates
1 Dec 2008to 31 Dec 2018
Phase
Observational
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 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study population: patients with advanced PD, responders to levodopa and with disabling motor fluctuations. that fulfilled the UK Brain Bank criteria (Hughes et al., 1992) for the diagnosis of idiopathic PD and were experiencing severe motor fluctuations, which were debilitating in daily life, despite receiving optimized conventional oral medications. Patients had been previously treated with oral levodopa combined with entacapone, rasagiline, dopamine agonists and/or apomorphine injections. Patients with atypical parkinsonian features were not included.

Who may be able to join

  • Patients with Parkinson's Desease (PD), diagnosed according to diagnostic criteria of the Brain Bank of London - United Kingdom Parkinson's disease Society Brain Bank (Gibb and Lees 1988; Hughes, Daniel et al. 1992; Calne, Snow et al 1992 ; Daniel i Lees 1993; Gelb, Oliver et al., 1999)
  • Patients with PD who respond to levodopa, according to the doctor's opinion. When the values of clinical scales with levodopa treatment achieve a 20-30% improvement in the scores of the Unified Parkinson's Disease Rating Scale (UPDRS). (UPDRS Off - UPDRS On) / UPDRS Off (Merello, Nouzeilles et al., 2002).
  • Patients with PD with a recognized Off and On status (motor fluctuations), confirmed by Parkinson's Disease Diary © (Hauser, Friedlander et al., 2000) at the start of the study (newspapers corresponding to 3 days preceding the initial visit).
  • Patients with PD in the advanced stage with severe motor fluctuations and dyskinesia induced by levodopa, poorly controlled with conventional optimized treatment.
  • Patients with PD in the advanced stage with severe motor fluctuations and dyskinesia induced by levodopa, poorly controlled with other complex treatments (such as apomorphine infusion pumps or ECP).
  • Patients with PD in the advanced state with serious motor fluctuations that present other non-motor complications such as depressive disorder, mild cognitive disorder, pulmonary control disorder, hallucinations and psychotic disorders and episodes of sleep, of moderate severity but , which excludes them from other alternatives to complex treatments, assisted with devices, second-line antiparkinsonians.
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  • Patients who are capable, they or their responsible carers and assistants, to learn the treatment with levodopa intestinal infusion and the use of their devices and to guarantee their proper functioning and correct handling.
  • Patients with PD who have been indicated and who have agreed to begin treatment with levodopa intestinal infusion.
  • Patients who have included and granted their consent to participate in the prospective study of habitual clinical practice and have signed an informed consent form to participate in the study.
  • Women who have stopped menstruation naturally 24 months before, or are surgically sterile.
  • Women of childbearing age may participate in the study provided they use a contraceptive method acceptable from a medical point of view (a stable dose of contraceptive drug for at least 3 months or barrier methods: intrauterine device, diaphragm, or combination of condoms and spermicide).
  • Women who are not nursing or are pregnant. Although no human teratogenicity has been described with levodopa treatment, and carbidopa does not cross the placental barrier and does not prevent these patients from interrupting oral levodopa during pregnancy (Merchant, Cohen et al., 1994; Ball i Sagar 1995; von Graevenitz, Shulman et al. 1996; Nomoto, Kaseda et al., 1997); In the event that it is considered GILC will start after pregnancy.
  • Patients attending the external consultation of the Neurology Service (Unit of Movement Disorders) at the Vall d'Hebron University Hospital.

Who cannot join

  • Patients who do not suffer from an idiopathic PD. That is, in which the diagnosis of PD is unclear or there is suspicion that there are other Parkinson's syndromes, such as secondary parkinsonism (caused by drugs, toxins, infectious agents, vascular disease, trauma or brain neoplasms), Parkinson plus syndromes (e.g., multi systemic atrophy, progressive supranuclear paralysis, corticosteroidal degeneration) or other neurodegenerative diseases.
  • Contraindications for the use of levodopa, such as narrow angle glaucoma, pheochromocytoma, Cushing syndrome or malignant melanoma history.
  • Treatment with non-selective MAO inhibitors and selective MAO type A inhibitors. These treatments should not be administered simultaneously with levodopa intestinal infusion. They must be taken down at least two weeks before the start of the treatment.
  • Psychiatric disorders, neurological or behavioral disorders that may interfere with the capacity of the subjects to give their informed consent to participate, or interfere with the performance or interpretation of the study; This category also includes serious hallucinations.
  • Cognitive deficiencies or dementias, defined as a score <24 in the Mini Mental State Exam (MMSE) (Folstein MF, Folstein et al., 1975) or that reach the criteria for the dementia of the Diagnostic and Statistical Manual of Fourth Mental Disorders (DSM-IV) (American Psychiatric Association 2000). Except for a compelling indication that the fluctuations are seriously impaired and correct and successful treatment and supervision can be guaranteed.
  • Abnormal laboratory data of clinical importance or any abnormal laboratory value that may interfere with the evaluation of safety according to the doctor.
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  • Current indications of haematological, autoimmune, endocrine, cardiovascular, renal or gastrointestinal disorders of clinical importance that could interfere with the participation of the subject in the study.
  • Background or current suffering of gastrointestinal, liver, kidney or other pathology that may interfere with the absorption, distribution, metabolism or excretion of the study's drug or its evaluation, or interfere with the introduction of the probe system.
  • Medical, laboratory or surgical problems that the doctor considers to be of clinical importance.
  • Subjects in which the placement of a GEP-J probe is contraindicated for treatment with levodopa intestinal infusion or subjects considered to be of high risk for the GEP-J procedure, according to the evaluation performed by the gastroenterologist or the surgeon.
  • The contraindications for the placement of the GEP-J probe include, among others, the following processes:
  • Pathological changes in the gastric wall.
  • Impossibility of joining the gastric wall and the abdominal wall.
  • Blood clotting disorders: prothrombin activity less than 60% or INR of 1.4 and platelet count less than 80,000; Anticoagulant or antiaggregant treatment is not a contraindication but should be corrected and suspended before the procedure, due to the risk of bleeding.
  • Pneumonia or severe respiratory failure. It has been suggested that a forced vital capacity of less than 1 liter and a pCO2 greater than 45 mmHg would be associated with an unacceptable mortality with the GEP procedure.
  • Ascites
  • Peritonitis
  • Acute pancreatitis.
  • Paralytic ileus.
  • State of immunodeficiency, neutropenia, HIV, hypogammaglobulinemia, chronic steroid therapy.
  • Except in cases where the indication of treatment with levodopa intestinal infusion is manifestly necessary and will be resorted to the implantation of a surgical gastrostomy.
  • Uncooperative attitude or reasonable probability that the subject does not comply with the treatment and the procedures of the study.
  • Subjects that do not provide their informed consent in writing to participate in the study.

Trial locations and contacts

1 site in 1 country.

Oriol de Fabregues, MD, PhD contact

00 34 934894258 ext. 4258

odfabregues@vhebron.net

Inmaculada Fuentes Camps, MD contact

00 34 934894113 ext. 4881

usic@vhir.org

Spain1 site, 1 recruiting

  • Hospital Universitari Vall d'Hebron

    Barcelona, 08035

    Oriol de Fabregues, MD, PhD, 00 34 934894258 ext. 4258, odfabregues@vhebron.net

    Inmaculada Fuentes Camps, MD, 00 34 4894113 ext. 4881, usic@vhir.org

    Recruiting

Other trials in Spain

About this study

Official title: Long-term Safety and Effectiveness in Motor and Non-motor Symptoms of Levodopa-carbidopa Intestinal Gel Infusion in Advanced Parkinson's Disease Patients With Motor Fluctuations

Levodopa-carbidopa intestinal gel (LCIG) infusion has demonstrated to improve motor fluctuations. The aim of this study is to assess the long-term safety and effectiveness of LCIG infusion in advanced Parkinson's disease (PD) patients with motor fluctuations and its effect in non-motor symptoms.

Read the detailed description

The following parameters were analyzed prior to LCIG treatment (at baseline), at months one, three, six and twelve, and every year afterwards over a 10-year period:

  • Safety:
  • Adverse Events (AEs) related to percutaneous endoscopic gastrostomy (PEG) procedures and gastrostomy, infusion device, and treatment. Actions taken to solve them, and reasons for treatment discontinuation and withdrawal.
  • Effectiveness:
  • Motor fluctuations: Off time in hours recorded in Parkinson's Disease Diary©.
  • Dyskinesia and other motor clinical aspects: evaluated with the Unified Parkinson's Disease Rating Scale (UPDRS) part IV, UPDRS part II in On and Off, UPDRS part III in On and Off, Hoehn and Yahr (H\&Y) stage in On and Off and Schwab and England (S\&E) scale.
  • Non-motor clinical aspects: cognitive function through Mini Mental State Examination (MMSE), and UPDRS part I, and relevant neuropsychiatric disorders.

The parameters analyzed in the three prospective substudies carried out in three subsets of this population, are described below:

Substudy 1 - Cognition and behavior assessment: Subgroup evaluated with a specific neuropsychological battery for assessment of cognition and behavior disorders prior to treatment (at baseline) and after 6 months of LCIG, by the same neuropsychologist at the same environmental conditions and in patients in phase On. The cognitive examination included: tests that assessed cognitive areas affected in PD according to the literature, psychometric tests with well-known parameters, tests that can be used in different types of populations (neurologic and psychiatric disorders, screening, etc.), tests suitable for a population with low educational and cultural level.

  • Attentional function: Forward Digit Span test of Weschler Adult Intelligence Scale-Third Edition (WAIS III); Audio-verbal attentional capacity; and Stroop Color-Word test.
  • Executive functions: Backward Digit Span of WAIS III; Audio-verbal working memory; Stroop-word and Stroop-color subtests; Response inhibition capacity; Controlled Oral Word-Association Test (FAS) of phonemic verbal fluency; Category Naming Test (Animals) of semantic verbal fluency.
  • Visual-constructional visuospatial and visuoperceptual functions: Clock Drawing Test - (order and copy) -visual-constructional; Reading clocks - simple visuospatial ability; Luria test of overlapping figures - visual perceptive skills function.
  • Memory and learning: Rey Auditory Verbal Learning Test (RAVLT) - Short and long term audio-verbal memory and recognition.
  • Language: Boston Naming Test (BNT) - Title by visual comparison.
  • Motor functions: Luria motor sequences - Voluntary motor control, Motor coordination.
  • Mood: Beck depression inventory (BDI)
  • Behavior: Neuropsychiatric Inventory (NPI) - Exploration of psychological and behavioral symptoms.

Substudy 2 - Quality of sleep: Subgroup evaluated with Epworth scale, fatigue scale, Pittsburg quality of sleep questionnaire, Beck Depression Inventory (BDI), and Hamilton anxiety scale, administered prior to treatment (at baseline) and 6 months after treatment. In addition, an overnight polysomnography (PSG) study was carried out at these timings.

Substudy 3 - Health status, QoL and caregiver burden: Subgroup evaluated for up to 12 months, with the Spanish version of the 39-items quality of life questionnaire in PD (PDQ-39, 0-156), health status questionnaires (EQ-5D, range 5-15; and EQ-VAS range 0-100), global clinical impression scale (CGI, range 1-7), and caregiver burden questionnaire or Zarit Burden index (ZBI, range 0-100). Assessments were done prior to treatment (at baseline), 1 week, 3 months, 6 months and 12 months after treatment.

Keywords
levodopa infusion
Medical subject headings
Parkinson Disease

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in motor fluctuations of the Off time.

    number of hours in Off time measured with Parkinson's Disease Diary © (Hauser, Friedlander et al., 2000). Changes will be compared to basal data.

    Measured: 10 years

Secondary outcomes (12)

  1. Change in proportion of the waking day with dyskinesia

    Measured with the proportion of the day (in percentage) with dyskinesia. Responding to question 32 of Unified Parkinson's Disease Rating Scale (UPDRS) part IV categorizing 5 possible percentages: 0=0%, 1=1-25%, 2=26-50%, 3=51-75%, 4=76-100%. Understanding that the highest percentage indicates more time of the day in this period (historical information). Changes will be compared to basal data.

    Measured: 10 years

  2. Change in severity of dyskinesia

    Measured with the level of disability caused by dyskinesia. Responding to question 33 of the Unified Parkinson's Disease Rating Scale (UPDRS) part IV that categorizes in 0: they are not disabling, 1: mildly disabling, 2: moderately disabling, 3: severely disabling and 4: they produce total disability. Changes will be compared to basal data.

    Measured: 10 years

  3. Change in parkinsonian motor symptoms assessed by the Unified Parkinson's Disease Rating Scale (UPDRS)

    Measured with the Unified Parkinson's Disease Rating Scale (UPDRS) ranging from 0 (normal) to 199 (highest motor disability). Changes will be compared to basal data.

    Measured: 10 years

  4. Change in Sleep Quality as assessed by Epworth Sleepines Scale (ESS)

    Measured with Epworth Sleepines Scale (ESS) ranging from 0 (normal) to 24 (highest sleepiness). Changes will be compared to basal data.

    Measured: 6 months

  5. Change in Sleep Quality as assessed by Pittsburgh Sleep Quality Index (PSQI)

    Measured with Pittsburgh Sleep Quality Index (PSQI), ranging from 0 (healthier sleep quality) to 21 (worst sleep quality). Changes will be compared to basal data.

    Measured: 6 months

  6. Total sleep time

    Total sleep time measured with an overnight polysomnography

    Measured: One night at the sleep unit

  7. Arousal index

    number of arousals/hour of sleep measured with an overnight polysomnography

    Measured: One night at the sleep unit

  8. Sleep architecture

    percentage of the different sleep phases measured with an overnight polysomnography

    Measured: One night at the sleep unit

  9. Change in cognitive function as assessed by the Unified Parkinson's Disease Rating Scale (UPDRS)

    Measured with the Unified Parkinson's Disease Rating Scale (UPDRS) Part I (mentation, behavior and mood) ranging from 0 (normal) to 16 (highest cognitive function impaired). Changes will be compared to basal data.

    Measured: 6 months

  10. Change in quality of life as assessed by 39-item Parkinson's disease Quality of Life Questionnaire Summary Index (PDQ-39)

    Measured with of the 39-item Parkinson's disease Quality of Life Questionnaire Summary Index (PDQ-39) ranging from 0 (normal) to 100 (worst quality of life). Changes will be compared to basal data.

    Measured: 1 year

  11. Change in caregiver burden as assessed by the Zarit caregiver Burden Index (ZBI)

    Measured with of the Zarit caregiver Burden Index (ZBI) ranging from 0 (no overburden) to 110 (totally overburden). Changes will be compared to basal data.

    Measured: 1 year

  12. Long term treatment safety as assessed by the ocurrence of serious advers events

    Collecting adverse event that causes death, threatens life, requires hospitalization or prolongs hospitalization, causes disability or constitutes an important medical event.

    Measured: 10 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Jul 2018
  2. Study start1 Dec 2008
  3. Primary completion18 Jul 2018
  4. Study completion31 Dec 2018 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
40 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03602924
Sponsor's protocol ID
PR(AG)129/2008
Status last verified
Jul 2018
First submitted
27 Jun 2018
Last updated
27 Jul 2018
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Undecided: Clinical Study report, results and statistical analysis, study protocol may be shared

Publications

  • Antonini A, Isaias IU, Canesi M, Zibetti M, Mancini F, Manfredi L, Dal Fante M, Lopiano L, Pezzoli G. Duodenal levodopa infusion for advanced Parkinson's disease: 12-month treatment outcome. Mov Disord. 2007 Jun 15;22(8):1145-9. doi: 10.1002/mds.21500.

    PubMed 17661426

  • Antonini A, Yegin A, Preda C, Bergmann L, Poewe W; GLORIA study investigators and coordinators. Global long-term study on motor and non-motor symptoms and safety of levodopa-carbidopa intestinal gel in routine care of advanced Parkinson's disease patients; 12-month interim outcomes. Parkinsonism Relat Disord. 2015 Mar;21(3):231-5. doi: 10.1016/j.parkreldis.2014.12.012. Epub 2014 Dec 19.

    PubMed 25585993

  • Buongiorno M, Antonelli F, Camara A, Puente V, de Fabregues-Nebot O, Hernandez-Vara J, Calopa M, Pascual-Sedano B, Campolongo A, Valldeoriola F, Tolosa E, Kulisevsky J, Marti MJ. Long-term response to continuous duodenal infusion of levodopa/carbidopa gel in patients with advanced Parkinson disease: The Barcelona registry. Parkinsonism Relat Disord. 2015 Aug;21(8):871-6. doi: 10.1016/j.parkreldis.2015.05.014. Epub 2015 May 19.

    PubMed 26003410

  • Caceres-Redondo MT, Carrillo F, Lama MJ, Huertas-Fernandez I, Vargas-Gonzalez L, Carballo M, Mir P. Long-term levodopa/carbidopa intestinal gel in advanced Parkinson's disease. J Neurol. 2014 Mar;261(3):561-9. doi: 10.1007/s00415-013-7235-1. Epub 2014 Jan 30.

    PubMed 24477490

  • Catalan MJ, de Pablo-Fernandez E, Villanueva C, Fernandez-Diez S, Lapena-Montero T, Garcia-Ramos R, Lopez-Valdes E. Levodopa infusion improves impulsivity and dopamine dysregulation syndrome in Parkinson's disease. Mov Disord. 2013 Dec;28(14):2007-10. doi: 10.1002/mds.25636. Epub 2013 Oct 10.

    PubMed 24123193

  • Eggert K, Schrader C, Hahn M, Stamelou M, Russmann A, Dengler R, Oertel W, Odin P. Continuous jejunal levodopa infusion in patients with advanced parkinson disease: practical aspects and outcome of motor and non-motor complications. Clin Neuropharmacol. 2008 May-Jun;31(3):151-66. doi: 10.1097/wnf.0b013e31814b113e.

    PubMed 18520982

  • Fasano A, Ricciardi L, Lena F, Bentivoglio AR, Modugno N. Intrajejunal levodopa infusion in advanced Parkinson's disease: long-term effects on motor and non-motor symptoms and impact on patient's and caregiver's quality of life. Eur Rev Med Pharmacol Sci. 2012 Jan;16(1):79-89.

    PubMed 22338551

  • Fernandez HH, Standaert DG, Hauser RA, Lang AE, Fung VS, Klostermann F, Lew MF, Odin P, Steiger M, Yakupov EZ, Chouinard S, Suchowersky O, Dubow J, Hall CM, Chatamra K, Robieson WZ, Benesh JA, Espay AJ. Levodopa-carbidopa intestinal gel in advanced Parkinson's disease: final 12-month, open-label results. Mov Disord. 2015 Apr;30(4):500-9. doi: 10.1002/mds.26123. Epub 2014 Dec 24.

    PubMed 25545465

  • Nyholm D, Lewander T, Johansson A, Lewitt PA, Lundqvist C, Aquilonius SM. Enteral levodopa/carbidopa infusion in advanced Parkinson disease: long-term exposure. Clin Neuropharmacol. 2008 Mar-Apr;31(2):63-73. doi: 10.1097/WNF.0b013e3180ed449f.

    PubMed 18382177

  • Olanow CW, Kieburtz K, Odin P, Espay AJ, Standaert DG, Fernandez HH, Vanagunas A, Othman AA, Widnell KL, Robieson WZ, Pritchett Y, Chatamra K, Benesh J, Lenz RA, Antonini A; LCIG Horizon Study Group. Continuous intrajejunal infusion of levodopa-carbidopa intestinal gel for patients with advanced Parkinson's disease: a randomised, controlled, double-blind, double-dummy study. Lancet Neurol. 2014 Feb;13(2):141-9. doi: 10.1016/S1474-4422(13)70293-X. Epub 2013 Dec 20.

    PubMed 24361112

  • Puente V, De Fabregues O, Oliveras C, Ribera G, Pont-Sunyer C, Vivanco R, Cucurella G, Giralt E, Delgado T, Garcia C, Seoane A, Campo R. Eighteen month study of continuous intraduodenal levodopa infusion in patients with advanced Parkinson's disease: impact on control of fluctuations and quality of life. Parkinsonism Relat Disord. 2010 Mar;16(3):218-21. doi: 10.1016/j.parkreldis.2009.07.015. Epub 2009 Sep 16.

    PubMed 19762271

  • Zibetti M, Merola A, Artusi CA, Rizzi L, Angrisano S, Reggio D, De Angelis C, Rizzone M, Lopiano L. Levodopa/carbidopa intestinal gel infusion in advanced Parkinson's disease: a 7-year experience. Eur J Neurol. 2014 Feb;21(2):312-8. doi: 10.1111/ene.12309. Epub 2013 Dec 7.

    PubMed 24313838

Questions about this trial

What is this clinical trial studying?

An observational study of Parkinson Disease, run by Hospital Universitari Vall d'Hebron Research Institute at 1 site in Spain.

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 13 inclusion and 23 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: status not confirmed, as of the sponsor's last update on 27 Jul 2018. 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 Spain. 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.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

Contact Oriol de Fabregues, MD, PhD (00 34 934894258 ext. 4258, odfabregues@vhebron.net), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in motor fluctuations of the Off time. (time frame: 10 years). 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 NCT03602924, which also lists 12 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 27 Jul 2018.

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