Status:
COMPLETED
Effect of Pioglitazone Administered to Patients With Adrenomyeloneuropathy
Lead Sponsor:
Pujol, Aurora, M.D.
Collaborating Sponsors:
Instituto de Salud Carlos III
Fundacion Hesperia
Conditions:
Adrenomyeloneuropathy
X-linked Adrenoleukodystrophy
Eligibility:
All Genders
18-65 years
Phase:
PHASE2
Brief Summary
X-linked adrenoleukodystrophy is a rare, demyelinating and neurodegenerative disorder, due to loss of function of a fatty acid transporter, the peroxisomal ABCD1 protein. Its more frequent phenotype, ...
Detailed Description
Proof of concept for this trial is provided by the results of biochemical, neuropathological and motor effects of pioglitazone in two mouse models of AMN. Pioglitazone was given orally (9 mg/kg/day) f...
Eligibility Criteria
Inclusion
- 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, γGT, 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
- 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
Key Trial Info
Start Date :
January 1 2016
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
July 1 2019
Estimated Enrollment :
18 Patients enrolled
Trial Details
Trial ID
NCT03864523
Start Date
January 1 2016
End Date
July 1 2019
Last Update
September 10 2019
Active Locations (2)
Enter a location and click search to find clinical trials sorted by distance.
1
Bellvitge University Hospital
L'Hospitalet de Llobregat, Barcelona, Spain, 08908
2
Donostia University Hospital
Donostia / San Sebastian, Spain, 20080