Clinical trial NCT06169046: A Placebo-controlled Study of Clenbuterol in Spinal and Bulbar Muscular Atrophy
Official title: A Placebo-controlled Study to Evaluate the Efficacy and Safety of Clenbuterol in Patients With Spinal and Bulbar Muscular Atrophy (SBMA)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Spinal and Bulbar Muscular Atrophy
Keywords: SBMA
clenbuterol
trial
Lead sponsor: University Hospital Padova
Sponsor class: OTHER
Collaborators: name: Mario Negri Institute for Pharmacological Research
First posted: 2023-12-13
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 2 parallel groups
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. males who have received a genetically confirmed diagnosis of SBMA (AR CAG repeat number \>= 38);
2. aged between 18 and 75 (+364 days) years;
3. displaying one or more of the following clinical symptoms: muscle atrophy, limb weakness, bulbar palsy;
4. able to walk independently with or without a cane or other supporting device (all supporting devices are acceptable except on wheelchair);
5. providing a written informed consent.

Exclusion Criteria:

1. a documented cardiovascular disease precluding the use of beta2 agonists (in the judgment of the investigators);
2. 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;
3. 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);
4. inability to walk or walking only with the support of a caregiver;
5. use of beta2 agonists in the preceding 6 months;
6. participation to an interventional trial in the preceding 3 months;
7. neuromuscular disease other than SBMA.

Primary outcomes:
measure: 6-minute-walk test
timeFrame: 48 weeks
Secondary outcomes:
measure: SBMA-FRS scale
timeFrame: 48 weeks
measure: Adult Myopathy Assessment Tool (AMAT)
timeFrame: 48 weeks
measure: FVC
timeFrame: 48 weeks
measure: 6K scale
timeFrame: 48 weeks
measure: Serum creatinine levels
timeFrame: 48 weeks
measure: ALSAQ-40
timeFrame: 48 weeks
measure: individualized neuromuscular quality of life (INQoL) questionnaire
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Padova
country: Italy
facility: Azienda Ospedale Università di Padova
state: PD
Study officials:
affiliation: Azienda Ospedale Università di Padova
name: Gianni Sorarù, MD
role: PRINCIPAL_INVESTIGATOR
References: