Study About Efficacy and Safety to Treat Multi-System-Atrophy

February 15, 2018 updated by: German Parkinson Study Group (GPS)

Double-Blind, Randomised, Two-Armed Study for the Evaluation of Efficacy and Safety of Minocycline for Treatment

Study Hypothesis:

- Does a treatment with Minocycline of 2 x daily 2 x 50 mg effect the progression of clinical symptoms and diagnosis in patients with MSA?

Background and Rationale:

  • The Parkinson-Syndrome which is characterised by the clinical triad akinesis, rigor and passive tremor, is caused by Parkinson's disease (PD) in about 70 % of the cases (Oertel et al., 2003). However, beside the Parkinson's disease there are several, to some extent rare, so-called atypical Parkinson's syndromes. The two most frequent of these atypical Parkinson-Syndromes are the
  • Multi-System-Atrophy (MSA) and the Progressive Supranuclear Palsy (PSP). Due to the often much varying courses and since they are not well known, these diseases are frequently diagnosed late or not diagnosed at all. Nevertheless, an early diagnosis is substantial for further treatment, since the prognosis and therapy of atypical Parkinson Syndromes differ essentially from those of PD. Whereas the neuronal death of cells in PD is restricted essentially to the Substantia nigra, a dominant destruction of neurons in brain stem, Cerebellum and Striatum additionally happens in cases of MSA and PSP.
  • Up to now no adequate treatment strategies are at disposal. Initially the giving of L-Dopa can lead to an improvement for < 10% of the patients only.
  • Minocycline is an antibiotic belonging to the group of the Tetracyclines.
  • Recently, it could be demonstrated that Minocycline has a neuroprotective impact besides the anti-inflammatory impact.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Study Hypothesis:

  • Does a treatment with Minocycline of 2 x daily 2 x 50 mg effect the progression of clinical symptoms and diagnosis in patients with MSA?
  • Minocycline is an antibiotic belonging to the group of the Tetracyclines. It is applied in treating bacterial infections and skin disorders (acne), but there are studies that prove a good effect on the inflammatory changes with rheumatoid arthritis (O´Dell, 1999; O´Dell et al., 2001; Pillemar et. al., 1997). In a four-years-lasting double-blind-placebo-controlled study it could be demonstrated that Minocycline represents an effective therapy for the seropositive rheumatoid arthritis. Moreover, during the long term therapy only a low side effect rate was observed (O´Dell et al., 1999; Langevitz et al., 2000; Alarcon, 2000).
  • Recently, it could be demonstrated that Minocycline has a neuroprotective impact besides the anti-inflammatory impact. In the focal and global animal stroke model there was a clearly reduced stroke volume during the treatment of Minocycline in comparison to an untreated group (Yrjanheikki, 1998; Yrjanheikki, 1999). These data were replicated by various groups, from our group as well (unpublished data). Furthermore, the neuroprotective impact of Minocycline was examined with a number of animal experiences (Chen et al., 2000; Zhu et al., 2002; Kriz et al. 2002, Sanchez et al., 2001; Van Den Bosch et al., 2002; Popovic et al., 2002): amyotrophic lateral sclerosis, M. Huntington, trauma, multiple sclerosis.In these trials it could be demonstrated that Minocycline slows down the neuronal cell death.
  • Recently, in cooperation with American colleagues we were able to demonstrate that Minocycline possesses a high neuroprotective potency in the MPTP-Mouse model, (an animal-model of Parkinson's disease, in which a degeneration of neuronal cells in the basal ganglia occurs (Lin et al., 2001; Du et al., 2001). Dependent on the applied dosage (30-120 mg/kg), a neuroprotection of up to 77% could be observed. In our results we could prove, that NO as well as Caspase-1 play an important role in the pathogenesis of cell death. Both, the expression of iNOS and the activation of Caspase-1 could be blocked in the presence of Minocycline in the animal-model and in further cell culture trials. In addition, there was a decrease of inflammatory microglia activation in the examined brain sections in the presence of Minocycline. Similar results could be presented from the study group Przedborski (Wu et al., 2002).
  • In various studies it could be demonstrated that the regulation of iNOS as well as the activation of Microglia at the MSA play an important role. This activation of Microglia in persons can be proved by Positron-emission-tomography (PET) with the Benzodiazepine-Ligands PK11195. PK11195 (1-(2-chlorophenyl)-N-methyl-N-(1-methylpropyl)-3isoquinoline- carboxamide) is a highly specific Ligand for peripheral Benzodiazepine-binding sites (PBBS) (Leong et al., 1996). As in a normal brain only a few binding sites for PK11195 can be verified, a significant increase of the PBBS-Expression by activated microglia after neuronal cell death can be verified (Gerhard et al., 2001).
  • The results of our examinations and the results out of literature suggest that Minocycline could also have an effect on neuro-degenerative diseases and particularly have an effect with MSA. In the USA a study already examining the impact of orally given Minocycline to patients with Chorea Huntington or amyotrophic lateral sclerosis is taking place. The National Institutes of Health (NIH) in the USA will perform a multicentre, double-blind study about the effect of Minocycline on Parkinson's Disease (NIH website, www.nih.gov).
  • In this study, the effectiveness of Minocycline on the progression of clinical symptoms of MSA shall be examined.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
60

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

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

  • Austria
      • Innsbruck, Austria, A-6020
        • Neurologische Klinik der Universität Innsbruck
  • Germany
      • Berlin, Germany, 13353
        • Neurologische Poliklinik, Charité Campus Virchow
      • Bonn, Germany, 53105
        • Neurologische Universitätsklinik am Klinikum der Friedrich-Wilhelm-Universität Bonn
    • Baden-Württemberg
      • Heidelberg, Baden-Württemberg, Germany, 69120
        • Universitätsklinikum Heidelberg, Neurologische Klinik
      • Tübingen, Baden-Württemberg, Germany, 72076
        • Universitätsklinikum Tübingen, Neurologische Klinik
    • Bayern
      • Würzburg, Bayern, Germany, 97080
        • Neurologische Klinik am Klinikum der BJM-Universität
    • Hessen
      • Kassel, Hessen, Germany, 34128
        • Paracelsus-Elena-Klinik
      • Marburg, Hessen, Germany, 35033
        • Neurologische Klinik der Philipps-Universität Marburg
    • Sachsen
      • Dresden, Sachsen, Germany, 01307
        • Neurologische Universitätsklinik, Universitätsklinikum Carl-Gustav-Carus der Technischen Universität Dresden
    • Schleswig-Holstein
      • Kiel, Schleswig-Holstein, Germany, 24105
        • Universitätsklinikum Schleswig-Holstein, Campus Kiel, Klinik für Neurologie

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

40 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • age ≥ 40 and <= 75 years
  • Diagnosis of MSA-P in accordance with consensus criteria (Gilman et al., 1999; appendix)
  • UMSARS IV <= 3
  • Patient must be capable of understanding informed consent
  • Written consent to participation in the study

Exclusion Criteria:

  • Diseases associated with a demential syndrome
  • Dimming of consciousness
  • Any other chronical inflammatory disease (Crohn's disease, ulcerative colitis, C.a. hepatitis, C.a. pancreatitis)
  • Any malignant tumour disease
  • Chronical alcohol addiction
  • Severe Diabetes mellitus Type I and II (HbA1c > 8 %)
  • AV-Block ≥ 2nd degree
  • Atrial flutter, atrial fibrillation
  • Tachycardia (> 100 bpm)
  • Bradycardia (< 60 bpm)
  • High-blood pressure (systolic > 180 mm Hg, diastolic: > 110 mg HG)
  • Heart insufficiency (NYHA >2)
  • Pericarditis, pericardial effusion
  • Heart attack within the last six months before inclusion in the study, ACVB, C.a. myocarditis
  • Severe kidney insufficiency (Creatinine >3 mg/dl; Urea > 150 mg/dl)
  • Hepatic insufficiency (GOT > 3 x ULN; GPT > 3 x ULN)
  • Ulcer disease
  • Pneumonia, meningitis within 12 weeks before inclusion into study
  • Any immunosuppressive or cytotoxic therapy within the last year before inclusion in study
  • Any antibacterial and antiviral therapy within the last six weeks before inclusion in the study
  • Any systemic fungal infection within the last year before inclusion in the study
  • Any positive family anamnesis for autoimmune diseases
  • Pregnancy or nursing
  • Severe psychiatric disease within the last six months requiring hospitalisation, attempted suicide in the anamnesis, florid psychosis
  • Seizure disorder
  • Concomitant taking of the following drugs: Riluzole, Carbamazepine, Phenytoine, Primidone, Colestyramine, activated charcoal, cumarin, Cyclosporine, Methotrexate, Methoxyflurane, Theophylline, Phenobarbital; or drug classes: Antacids (containing Al, Mg, Ca), Retinoids, Digitalis Glycosides
  • Known hypersensitivity against Minocycline or other Tetracyclines
  • Simultaneous participation in another clinical trial

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: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Change in motor function: Difference between the UMSARS II baseline score and the UMSARS II score 48 weeks after start of therapy

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Difference between the UMSARS II baseline score and the UMSARS II score 24 weeks after start of therapy
Difference between the UMSARS I, III, IV baseline score and the UMSARS I, III, IV score 24 and 48 weeks after start of therapy
Difference between the UPDRS I-III baseline score and the UPDRS I-III score 24 and 48 weeks after start of therapy
Difference between the SF-12 baseline score and the SF-12 score 24 and 48 weeks after start of therapy
Difference between the EQ-5D baseline score and the EQ-5D score 24 and 48 weeks after start of therapy

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
German Parkinson Study Group (GPS)

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Competence Network on Parkinson's Disease
European MSA-Study Group
Federal Institute of Education and Sience

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Wolfgang H. Oertel, Prof. Dr., Neurologische Klinik der Philipps-Universität Marburg
  • Study Director: Richard Dodel, PD Dr., Neurologische Klinik, Rheinische Friedrich-Wilhelms-Universität Bonn
  • Study Chair: Werner Poewe, Prof. Dr., Neurologische Klinik der Universität Innsbruck
  • Study Chair: Gregor Wenning, Prof. Dr., Neurologische Klinik der Universität Innsbruck

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.

Helpful Links

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

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2003

Study Completion

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2005

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 31, 2005

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 3, 2005

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 7, 2005

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 19, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 15, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MEMSA-Study
  • Grant 01 GI 0201/01 GI 0401

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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