Effect of Pioglitazone Administered to Patients With Adrenomyeloneuropathy

NCT03864523 | Completed Phase 2

• 1 other identifier: XAMNPIOAP2011
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 2

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, the adrenomyeloneuropathy in adults, is characterized by axonal degeneration in spinal cord, spastic paraparesis and a disabling peripheral neuropathy. Actually, there is no efficient treatment for the disease. The work of the researchers in the last twelve years dissecting the physiopathological basis of the disorder has uncovered an involvement of the early oxidative stress in the neurodegenerative cascade and mitocondrial depletion. In a preclinical trial they have observed that pioglitazone, a PPARγ/PGC-1α axis metabolic activator with immunomodulatory, anti-inflammatory and antioxidant response regulator properties, efficiently reverse the clinical symptoms and the axonal degeneration in the mouse model for the disease and normalize stress and mitochondrial depletion biomarkers. The researchers will test the effectiveness of the drug in terms of motor function and correction of oxidative damage markers in proteins and DNA and inflammation markers in an open trial. Fifteen-twenty patients will be included and clinically explored and assessed in the HU of Bellvitge and the HU of Donostia using clinical scales for spasticity, evoked potentials, electroneurinograms and cranial RMN. The information will be collected in a data base that will be of great value to improve the present attention and the future follow-up of the patients and to facilitate their inclusion in therapeutic randomized, double blind, against placebo, multicentric and international clinical trials.

Conditions

Adrenomyeloneuropathy; X-linked Adrenoleukodystrophy

Keywords

AMN; pioglitazone

Outcome Measures

Primary Outcomes (1)

• 2 Minute Walk Test (2MWT)

  The score at this test corresponds to the distance traveled by the patient during 2 minutes, on a flat surface

  24 months

Secondary Outcomes (55)

• Timed Up and Go (TUG) test

  24 months

• Time to walk 25 Feet (TW25)

  24 months

• 6 Minute Walk Test (6MWT)

  24 months

• Sensory disturbances: tactile

  24 months

• Sensory disturbances: painful

  24 months

Study Arms (1)

XAMNPIO

EXPERIMENTAL

Pioglitazone 15 mg tablets 2/day during 2 years

Drug: Pioglitazone

Interventions

Pioglitazone DRUG

XAMNPIO

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Pujol, Aurora, M.D.: lead
• Instituto de Salud Carlos III: collaborator
• Fundacion Hesperia: collaborator
• ELA España Association: collaborator

Study Sites (2)

Bellvitge University Hospital

L'Hospitalet de Llobregat, Barcelona, 08908, Spain

Location

Donostia University Hospital

Donostia / San Sebastian, 20080, Spain

Location

MeSH Terms

Conditions

Adrenoleukodystrophy

Interventions

Pioglitazone

Condition Hierarchy (Ancestors)

Brain Diseases, Metabolic, Inborn; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hereditary Central Nervous System Demyelinating Diseases; Leukoencephalopathies; Demyelinating Diseases; X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System; Metabolism, Inborn Errors; Peroxisomal Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Adrenal Insufficiency; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDIV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 16, 2016
• First Posted: March 6, 2019
• Study Start: January 1, 2016
• Primary Completion: March 1, 2019
• Study Completion: July 1, 2019
• Last Updated: September 10, 2019

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

ES (2)