Effect of Pioglitazone Administered to Patients With Adrenomyeloneuropathy

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT03864523
• Date of registration: 16/09/2016
• Prospective Registration: No
• Primary sponsor: Onofre, Aurora Pujol, M.D.
• Public title: Effect of Pioglitazone Administered to Patients With Adrenomyeloneuropathy XAMNPIOP2011
• Scientific title: Effect of Pioglitazone Administered to Patients With Adrenomyeloneuropathy: a Phase II, Single-arm, Multicentric Clinical Trial
• Date of first enrolment: January 2016
• Target sample size: 18
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03864523
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

Spain

Key inclusion & exclusion criteria

Inclusion Criteria:

- 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 2MWT

- Normal brain MRI or brain MRI showing abnormalities that can be observed in AMN
patients without cerebral form of X-ALD with a maximum Loes score of 4

- Ejection fraction > 50% at echocardiogram

- Normal electrocardiogram

- Normal urine cytology

- Normal liver function, as assessed by plasma ASAT, ALAT, PAL, ?GT, bilirubin measures
(=2.5-fold normal values)

- Normal kidney function as assessed by plasma urea, creatinin (= 2-fold normal values)

- Appropriate steroid replacement if adrenal insufficiency is present

- Informed consent

- Affiliated to the Spanish Public Health System

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

- Brain MRI abnormalities of the "AMN type" with a Loes score > 4

- Any abnormal hypersignal of white matter visible on FLAIR sequences other than of "AMN
type" and related to X-ALD

- Patients taking pioglitazone or another glitazone during the past 6 months

- Diabetic patients (type I or II)

- Fasting blood glucose > 125 mg/L

- Glycosylated hemoglobin > 6%

- History of heart failure

- Heart failure (NYHA III to IV) or ejection fraction = 50%

- History of cardiac disease

- [Hemoglobin] < 13g/dl in males, <12 g/dl in women

- Absolute neutrophil count (ANC) <1500 cells/mm3

- Platelet count <100,000 cells/mm3

- Significant peripheral edema (2+ or more on the Assessment Chart for Pitting Edema) of
the extremities of any etiology

- Any evolutive malignancy during the last five years

- Prior or current bladder cancer

- Smokers (one pack/ day or more for at least 20 years), current or former

- Women with history of osteoporosis

- Menopaused woman with T-score < -2.5 on osteodensitometry measurement

- Any evolutive medical disease other than AMN

- Any psychiatric disease

- Pregnant or breastfeeding woman

- Either no pre-menopaused woman or no menopaused woman not taking any contraceptive
method

- Hereditary intolerance to galatose, or malabsorption of glucose or galactose due the
presence of monohydrated lactose.

- Hypersensibility to the active substance or to galactose (excipient)

- Concomitant treatment with cytochrome P450 CYP 2C8 inhibitors (e.g. gemfibrozil) or
inducers (e.g. rifampicin)

- Taking of either vitamin A, E or lipoic acid during the past 3 months

- Contraindications for MRI procedure such as subjects with paramagnetic materials in
the body, such as aneurysm clips, pacemakers, intraocular metal or cochlear implants

- Present participation to another therapeutic clinical trial for ALD

- Not easily contactable by the investigator in case of emergency or not capable to call
the investigator

- Gross hematuria of unknown origin



Age minimum: 18 Years
Age maximum: 65 Years
Gender: All

Health Condition(s) or Problem(s) studied

Adrenomyeloneuropathy

X-linked Adrenoleukodystrophy

Intervention(s)

Drug: Pioglitazone

Primary Outcome(s)

2 Minute Walk Test (2MWT) [Time Frame: 24 months]

Secondary Outcome(s)

Markers of inflammation: GPX4 [Time Frame: 24 months]

Markers of inflammation: IL8 [Time Frame: 24 months]

Markers of oxidative stress: CEL [Time Frame: 24 months]

Motor Evoked Potentials (MEP): Central motor conduction time [Time Frame: 24 months]

Revised Faecal Incontinence Scale (RFIS) [Time Frame: 24 months]

Sensory disturbances: painful [Time Frame: 24 months]

Sensory disturbances: tactile [Time Frame: 24 months]

SF-Qualiveen [Time Frame: 24 months]

Brainstem Auditory Evoked Potentials (BAEP): Latency III wave [Time Frame: 24 months]

Brainstem Auditory Evoked Potentials (BAEP): Latency III-V wave [Time Frame: 24 months]

Diffusion tensor Imaging (DTI) [Time Frame: 24 months]

Markers of inflammation: CXCL5 [Time Frame: 24 months]

Markers of inflammation: HGF [Time Frame: 24 months]

Markers of inflammation: IL9R [Time Frame: 24 months]

Markers of inflammation: TNF [Time Frame: 24 months]

Markers of oxidative stress: 8-oxoDG [Time Frame: 24 months]

Dynamometer test (optional) [Time Frame: 24 months]

Markers of oxidative stress: CML [Time Frame: 24 months]

Motor Evoked Potentials (MEP): Amplitude [Time Frame: 24 months]

Nerve conduction studies: amplitude of the signal in the sura sensitive nerve [Time Frame: 24 months]

Nerve conduction studies: conduction velocity in the peroneal nerve [Time Frame: 24 months]

Somatosensory Evoked Potentials (SSEP): Latency N20 [Time Frame: 24 months]

Expanded disability status scale (EDSS) [Time Frame: 24 months]

Markers of inflammation: CCR3 [Time Frame: 24 months]

Brainstem Auditory Evoked Potentials (BAEP): Latency I-V wave [Time Frame: 24 months]

Markers of inflammation: adiponectin [Time Frame: 24 months]

Markers of inflammation: IL6 [Time Frame: 24 months]

Markers of inflammation: MCP-1 [Time Frame: 24 months]

6 Minute Walk Test (6MWT) [Time Frame: 24 months]

Conventional MRI [Time Frame: 24 months]

Brain MRI spectroscopy (MRS) [Time Frame: 24 months]

Brainstem Auditory Evoked Potentials (BAEP): Latency I wave [Time Frame: 24 months]

Markers of inflammation: NGF [Time Frame: 24 months]

Markers of oxidative stress: GSA [Time Frame: 24 months]

Markers of inflammation: PPARd [Time Frame: 24 months]

Markers of oxidative stress: MDAL [Time Frame: 24 months]

Somatosensory Evoked Potentials (SSEP): Latency N22 [Time Frame: 24 months]

Somatosensory Evoked Potentials (SSEP): Latency N8 [Time Frame: 24 months]

Brainstem Auditory Evoked Potentials (BAEP): Latency V wave [Time Frame: 24 months]

Motor Evoked Potentials (MEP): F wave [Time Frame: 24 months]

Nerve conduction studies: conduction velocity in the sura sensitive nerve [Time Frame: 24 months]

Time to walk 25 Feet (TW25) [Time Frame: 24 months]

Motor Evoked Potentials (MEP): Central latency [Time Frame: 24 months]

Somatosensory Evoked Potentials (SSEP): Amplitude N20 [Time Frame: 24 months]

Somatosensory Evoked Potentials (SSEP): Amplitude N40 [Time Frame: 24 months]

Somatosensory Evoked Potentials (SSEP): Latency N9 [Time Frame: 24 months]

Sensory disturbances: vibratory [Time Frame: 24 months]

Somatosensory Evoked Potentials (SSEP): Latency N13 [Time Frame: 24 months]

Somatosensory Evoked Potentials (SSEP): Latency P40 [Time Frame: 24 months]

Ashworth scale [Time Frame: 24 months]

Brainstem Auditory Evoked Potentials (BAEP): Latency I-III wave [Time Frame: 24 months]

Markers of inflammation: CXCL9 [Time Frame: 24 months]

Markers of inflammation: STAT1 [Time Frame: 24 months]

Timed Up and Go (TUG) test [Time Frame: 24 months]

Nerve conduction studies: amplitude of the signal in the peroneal motor nerve [Time Frame: 24 months]

Secondary ID(s)

XAMNPIOAP2011

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Fundacion Hesperia

Instituto de Salud Carlos III

ELA España Association