Therapeutic Metabolic Intervention in Patients With Spastic Paraplegia SPG5

Study Overview
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Brief Summary
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The purpose of this project is to study the efficacy of three candidate molecules (Xenbilox, Tahor and Resveratrol) in order to decrease the production of oxysterols by reducing the synthesis of cholesterol and/or regulate the production of bile acids and/or enabling neuroprotective action within the motor neuron.

Detailed Description
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The primary objective of the study is: - decrease the accumulation of metabolites which can have a negative impact on neurological and systemic function of patients with SPG5. The secondary objectives of the study are: confirm the clinical and biological tolerance of the different candidate molecules under study improve the serum bile acid profile of patients with SPG5

Official Title
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Therapeutic Metabolic Intervention in Patients With Spastic Paraplegia SPG5

Conditions
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Spastic Paraplegia, Hereditary

Intervention / Treatment
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* Drug: Xenbilox
* Dietary Supplement: Resveratrol
* Drug: Tahor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: patients that have confirmed through genetic testing their status as carriers of 2 mutations in the CYP7B1 gene age ≥ 18 years patients that have signed the informed consent form presence of health care coverage Exclusion Criteria: known hypersensitvity to chenodeoxycholic acid, atorvastatin, resveratrol or to any of their byproducts cholesterol lowering medications other than the study treatment hepatic failure with transaminases >3 times the normal level progressive biliary pathology chronic diarrhea serious mental illness significant comorbid neurological disorder incapacity to understand information about the protocol unwilling or unable to participate in any part of the study participation in another clinical trial during the study period person deprived of liberty by judicial or administrative decision adult subject under legal protection or unable to consent pregnant or breastfeeding women lack of health care coverage absence of a signed informed consent form

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Xenbilox<br>Xenbilox (chenodeoxycholic acid) 1000mg capsule by mouth every day for 2 months | Drug: Xenbilox<br> <br> * Other names: Chenodeoxycholic acid;|
| Active Comparator: Resveratrol<br>Resveratrol 80mg capsule by mouth every day for 2 months | Dietary Supplement: Resveratrol<br> <br> |
| Active Comparator: Tahor<br>Tahor (atorvastatin) 40mg tablet by mouth every day for 2 months | Drug: Tahor<br> <br> * Other names: Atorvastatin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of 27-hydroxycholesterol blood level after 2 months of treatment for each treatment | 27-hydroxycholesterol will be measured on fasten blood samples for the 12 patients included before and after the 2-month treatment period for each treatment | 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Modification of the serum acid profile after a 2-month treatment measured in blood and urine samples | In blood and urines samples of the 12 patients, the following criteria will be assesed in order to observe an evolution of the acid profile: total biliary acids ratio of primary/secondary biliary acids the ratio cholic acids/chenodeoxycholic acids the ratio chenodeoxycholic acids/ lithocholic acids | 2 months | 
| Change of 25-hydroxycholesterol blood level after 2 months of treatment for each treatment | 25-hydroxycholesterol will be measured on fasten blood samples for the 12 patients included before and after the 2-month treatment period for each treatment | 2 months | 
| Number of participants with adverse events related with digestive problems | During the study, adverse events related with digestive problems will be evaluate in order to asses the clinical tolerance to each treatment | 18 months | 
| Number of partcipants with adverse events related with standard biological parameters | Biological tolerance will be evaluate on patients blood samples at each visit. The following criteria will be assessed: ionogram and fasting glucose kidney and liver function with urea, creatinine,lipase, amylase, bilirubine, creatine phosphokinase, transaminases,sodium, potassium, calcium, phosphorus | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metabolism, spastic paraplegia, oxysterols, neurogenetics