Ignite Creation Date:
2024-05-05 @ 11:50 AM
Last Modification Date:
2024-10-26 @ 9:14 AM
Study NCT ID:
NCT00146809
Status:
COMPLETED
Last Update Posted:
2018-02-19
First Post:
2005-08-31
Brief Title:
Study About Efficacy and Safety to Treat Multi-System-Atrophy
Sponsor:
German Parkinson Study Group GPS
Organization:
German Parkinson Study Group GPS
Study Overview
Official Title:
Double-Blind Randomised Two-Armed Study for the Evaluation of Efficacy and Safety of Minocycline for Treatment
Status:
COMPLETED
Status Verified Date:
2018-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
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 Parkinsons disease PD in about 70 of the cases Oertel et al 2003 However beside the Parkinsons disease there are several to some extent rare so-called atypical Parkinsons 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
- 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 Parkinsons disease PD in about 70 of the cases Oertel et al 2003 However beside the Parkinsons disease there are several to some extent rare so-called atypical Parkinsons 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
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 ODell 1999 ODell 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 ODell 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 sclerosisIn 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 Parkinsons 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 mgkg 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 Parkinsons Disease NIH website wwwnihgov
In this study the effectiveness of Minocycline on the progression of clinical symptoms of MSA shall be examined
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 ODell 1999 ODell 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 ODell 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 sclerosisIn 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 Parkinsons 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 mgkg 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 Parkinsons Disease NIH website wwwnihgov
In this study the effectiveness of Minocycline on the progression of clinical symptoms of MSA shall be examined
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| Grant 01 GI 020101 GI 0401 | None | None | None |