Effect of pioglitazone in patienst with Adrenomyeloneuropathy.

• Register: EUCTR
• Last refreshed on: 26 November 2013
• Main ID: EUCTR2011-006113-34-ES
• Date of registration: 12/09/2013
• Prospective Registration: Yes
• Primary sponsor: AURORA PUJOL ONOFRE
• Public title: Effect of pioglitazone in patienst with Adrenomyeloneuropathy.
• Scientific title: Effect of pioglitazone administred to patients with Adrenomyeloneuropathy: A phase II, Singlearm, Monocentric Trial. - Pioglitazone in Adrenomyeloneuropathy
• Date of first enrolment: 24/10/2013
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-006113-34
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no Randomised: no Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no

Countries of recruitment

Spain

Contacts

• Name: AURORA PUJOL ONOFRE
• Affiliation: Idibell (Institut d'Investigació Biomèdica de Bellvitge)

• Name: AURORA PUJOL ONOFRE
• Affiliation: Idibell (Institut d'Investigació Biomèdica de Bellvitge)

Key inclusion & exclusion criteria

Inclusion criteria:
Men and women of 18 to 65 years old, inclusive.Clinical signs of AMN with at least pyramidal signs in the lower limbs and difficulties to run.Presence of motor deficit according to the EDSS scale. Ability to perform the 6MWT
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 20
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Gadolinium enhancement on T1 sequence of any abnormal hypersignal of white matter, including myelinated pyramidal tracts, visible at brain MRI on FLAIR sequences.History of heart failure or cardiac disease.Prior or current bladder cancer. Women with history of osteoporosis. Gross hematuria of unknown origin.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

X-linked adrenoleukodystrophy

Intervention(s)

Pharmaceutical Form: Tablet
INN or Proposed INN: PIOGLITAZONE
CAS Number: 111025-46-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 30-

Primary Outcome(s)

Main Objective: The primary goal of the trial is to show that pioglitazone treatment will provide clinical benefits in terms of functional capacity in the 20 enrolled AMN patients. Clinical benefits will be primarily measured by changes in the 6 Minutes Walking test, the primary efficacy endpoint.

Primary end point(s): The main efficacy evaluation criterion is changes in the 6 Minute Walk Test (6MWT) between M0 and M24. The score at this test corresponds to the distance traveled by the patient during 6 minutes, on a flat surface. Details about the 6MWT are given in 9.1.

Timepoint(s) of evaluation of this end point: Evaluation will be done at the beginning (M0) and at the end (M24) of the trial.

Secondary Objective: The secondary goal of the trial is the assessment of efficacy and safety of the proposed treatment in 20 patients with AMN. Efficacy will be measured in terms of motor function, quality of life, neuroimagery, evoked potentials, ENG/EMG and biological markers. Safety will be evaluated by clinical, biological and brain imaging exams and recording of any adverse event.

Secondary Outcome(s)

Secondary end point(s): Secondary efficacy endpoints consist in:
1) Tests evaluating the motor functions of treated AMN patients. They include: the Timed Up and Go (TUG) test, and evaluation of muscle strength by the use of a dynamoter on M0, M6, M12, M18 and M24 and the Spastic Paraplegia Rating Scale (SPRS) on M0, M12 and M24.
2) Quality of life: score of the Multiple Sclerosis Impact Scale (MSIS?29) questionnaire on M0 and M24.
3) Neuroimagery: a) brain abnormalities (hypersignal of pyramidal tracts, cerebellar and cerebral atrophy) on conventional MRI that will be assessed by the Loes score; b) diffusion tensor imaging (DTI) parameters in the cervical spinal cord and brain; c) and magnetic resonance spectroscopy (MRS) parameters in the cerebral white matter on M0 and M24. Tests performed in the Hospital Universitari de Bellvitge during the period of one year before the start of the trial will be considered valid.
4) Evoked potentials: visual, auditory, somatosensory, motor and laser evoked potentials will be studied at the beginning (M0) and at the end of the trial (M24). Tests performed in the Hospital Universitari de Bellvitge during the period of one year before the start of the trial will be considered valid.
5) ENG/EMG: nerve conduction velocity (NCV), amplitude of sensory potential (SNAP) in sensory nerves and motor evoked potential amplitude (CMAP) in motor nerves of the upper and lower extremities will be recorded on M0 and M24. Tests performed in the Hospital Universitari de Bellvitge during the period of one year before the start of the trial will be considered valid.
6) Biological measures:
- Markers of oxidative stress: GSA, CEL, MDAL, and CML in plasma and/or peripheral blood mononuclear cells and cerebrospinal fluid (only in patients who voluntarily agree) and 8oxo-dG in urine. Markers in plasma/PBMC/urine will be measured on M0, M6 and M24. Markers in CSF will be measured on M0 and M24.
- Markers of inflammation: CCR3, CXCL5, CXCL9, IL9R, PPARd, GPX4 and STAT1 in RNA obtained from MNC and HGF, IL6, IL8, MCP-1, NGF, TNF and adiponectin in plasma.

Timepoint(s) of evaluation of this end point: 1) Timed Up and Go (TUG) test, and evaluation of muscle strength by the use of a dynamoter on M0, M6, M12, M18 and M24 and the Spastic Paraplegia Rating Scale (SPRS) on M0, M12 and M24.
2) Quality of life: MSIS?29 on M0 and M24.
3) Neuroimagery: MRI, DTI, MRS on M0 and M24.
4) Evoked potentials: M0 and M24
5) ENG/EMG: M0 and M24
6) Biological measures:
- Markers of oxidative stress: on M0, M6 and M24 (markers in CSF will be measured on M0 and M24)
- Markers of inflammation: on M0, M6 and M24

Secondary ID(s)

XAMNPIOAP2011

Source(s) of Monetary Support

ELA Research Foundation

Fundación Hesperia