Rapamycin Treatment for ALS

• Status: Active, not recruiting
• Trial end date: 2021-09-15
• Target enrollment: 0
• Participant gender: All

Summary

In the last years research has pointed out potential mechanisms of pathogenesis in ALS including lack of degradation of abnormally accumulated proteins inside motor neurons, and an unbalanced function of the immune system leading to the prevalence of a neurotoxic function over neuroprotection. These two mechanisms contribute to ALS progression hence representing important therapeutic targets to modify disease expression.

With a phase II clinical trial the investigators aim to study the biological response in ALS treated with Rapamycin, to obtain predictive information for a larger study.

Eight Italian Centres will enroll 63 patients; treatment will be double blinded to patients and physicians, and will last 18 weeks.Follow up will be carried out for 36 months (total duration: 54 weeks).

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Azienda Ospedaliera - Universitaria di Modena; Azienda Ospedaliero-Universitaria di Modena
• Collaborators: Azienda Ospedaliera Niguarda Cà Granda; Azienda Ospedaliero Universitaria Maggiore della Carita; Fondazione I.R.C.C.S. Istituto Neurologico Carlo Besta; Fondazione Salvatore Maugeri; IRCCS Azienda Ospedaliera Universitaria San Martino - IST Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy; University of Modena and Reggio Emilia; University of Padova; University of Turin, Italy
• Treatments: Everolimus; Sirolimus

Criteria

Inclusion criteria:

• Patient diagnosed with a laboratory supported , clinically "probable" or "definite" amyotrophic lateral sclerosis according to the Revised El Escorial criteria (Brooks, 2000)

• Familial or sporadic ALS

• Female or male patients aged between 18 and 75 years old

• Disease duration from symptoms onset no longer than 18 months at the screening visit

• Patient treated with a stable dose of Riluzole (100 mg/day) for at least 30 days prior to screening

• Patients with a weight > 50 kg and a BMI ≥18

• Patient with a FVC ≥ 70 % predicted normal value for gender, height, and age at the screening visit

• Patient able and willing to comply with study procedures as per protocol

• Patient able to understand, and capable of providing informed consent at screening visit prior to any protocol-specific procedures

• Use of effective contraception both for males and females

Exclusion Criteria:

• Prior use of Sirolimus

• Prior allergy/sensitivity to Sirolimus or macrolides

• Any medical disorder that would make immunosuppression contraindicated, including but not limited to, acute infections requiring antibiotics, patients with known diagnosis of HIV, tuberculosis, hepatitis B or C infection or history of malignancy

• Severe comorbidities (heart, renal, liver failure), autoimmune diseases or any type of interstitial lung disease

• White blood cells<4,000/mm³, platelets count<100,000/mm³, hematocrit<30%

• Patient who underwent non invasive ventilation, tracheotomy and /or gastrostomy

• Women who are pregnant or breastfeeding

• Participation in pharmacological studies within the last 30 days before screening

• Patients with known superoxide dismutase 1 (SOD1) mutation or with familial ALS and a family member carrying SOD1 mutation.