A Placebo-controlled Study of Clenbuterol in Spinal and Bulbar Muscular Atrophy

Study Overview
=================
Brief Summary
-----------------
There is no cure to arrest or delay SBMA progression. It is estimated that  1000 individuals are affected by SBMA in Italy at any given time (prevalence: 1.5/100000) with an annual incidence of 0.19/100000 males. Here, we are going to test the potential of beta2-agonist stimulation on muscle as a therapeutic avenue for SBMA. We have provided pre-clinical evidence that β-agonist stimulation may be a therapeutic strategy for SBMA. Moreover, we have shown that beta2-agonists are effective in improving motor function without relevant adverse events in a small cohort of SBMA patients. To establish safety and efficacy of clenbuterol as a cure for SBMA, we are conducting a multicenter, phase II, randomized, double-blind, parallel-group, single dose, placebo-controlled trial. Indeed, based on our preliminary data, some concerns remain to be addressed.

Official Title
-----------------
A Placebo-controlled Study to Evaluate the Efficacy and Safety of Clenbuterol in Patients With Spinal and Bulbar Muscular Atrophy (SBMA)

Conditions
-----------------
Spinal and Bulbar Muscular Atrophy

Intervention / Treatment
-----------------
* Drug: Clenbuterol
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: males who have received a genetically confirmed diagnosis of SBMA (AR CAG repeat number >= 38); aged between 18 and 75 (+364 days) years; displaying one or more of the following clinical symptoms: muscle atrophy, limb weakness, bulbar palsy; able to walk independently with or without a cane or other supporting device (all supporting devices are acceptable except on wheelchair); providing a written informed consent. Exclusion Criteria: a documented cardiovascular disease precluding the use of beta2 agonists (in the judgment of the investigators); glaucoma, severe prostatic hypertrophy, hyperthyroidism, pheochromocytoma, and other medical conditions that, in the judgment of the investigators, would expose the patient to undue risk of harm or prevent the patient from completing the study; concomitant treatment with either beta-blockers or sympathomimetic drugs (If a beta-blockers concomitant medication is ongoing before the study inclusion, the patient can be enrolled if the beta-blocker is discontinued for 3 weeks prior to randomization visit); inability to walk or walking only with the support of a caregiver; use of beta2 agonists in the preceding 6 months; participation to an interventional trial in the preceding 3 months; neuromuscular disease other than SBMA.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 2 parallel groups
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: clenbuterole<br>45 patients will receive Clenbuterol at a final dosage of 0.04 mg/day, treated for a total of 48 weeks | Drug: Clenbuterol<br>* tablets<br>* Other names: active;|
| Placebo Comparator: placebo<br>45 patients will receive placebo, treated for a total of 48 weeks | Drug: Placebo<br>* tablets<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 6-minute-walk test | to assess the efficacy of chronic treatment with clenbuterol in patients with SBMA by the 6MW test | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SBMA-FRS scale | SBMA-FRS total score during the 12-months treatment period (from V2 to V7) in the two treatment arms | 48 weeks | 
| Adult Myopathy Assessment Tool (AMAT) | AMAT total score during the 12-months treatment period (from V2 to V7) in the two treatment arms | 48 weeks | 
| FVC | FVC during the 12-months treatment period (from V2 to V7) in the two treatment arms | 48 weeks | 
| 6K scale | 6K total score during the 12-months treatment period (from V2 to V7) in the two treatment arms | 48 weeks | 
| Serum creatinine levels | serum creatinine levels during the 12-months treatment period (from V2 to V7) in the two treatment arms | 48 weeks | 
| ALSAQ-40 | ALSAQ-40 total score during the 12-months treatment period (from V2 to V7) in the two treatment arms | 48 weeks | 
| individualized neuromuscular quality of life (INQoL) questionnaire | INQOL total score during the 12-months treatment period (from V2 to V7) in the two treatment arms | 48 weeks | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
SBMA, clenbuterol, trial