Rapamycin Treatment for ALS

NCT03359538 | Completed Phase 2 DMC

• 1 other identifier: RAP-ALS
• Study Type: interventional
• Target: 63
• Locations: 1 country
• Sites: 7

Brief 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).

Conditions

Amyotrophic Lateral Sclerosis

Keywords

Amyotrophic Lateral Sclerosis; Motor Neuron Disease; Rapamycin

Outcome Measures

Primary Outcomes (1)

• T-reg number

  Proportion of patients exhibiting a positive response (considered as increase in Treg of at least 30%), comparing baseline and treatment end between Rapamycin and placebo arm

  comparison between baseline and treatment end (week 18)

Secondary Outcomes (11)

• Number of serious adverse events (SAEs) and AEs in placebo and treatment arms

  At week 18 and 54

• Rapamycin capacity to pass through blood brain barrier

  At week 18

• Rapamycin efficacy in inhibiting Mtor pathway

  At week 8-18-30-54

• Changes in activation and homing capabilities of different T, B, natural killer (NK) cell subpopulations

  At baseline and at week 8-18-30-54

• Changes in CSF neurofilaments

  Baseline and week 18

Study Arms (3)

placebo

PLACEBO COMPARATOR

Patients assigned to this arm will take Riluzole as usual + placebo tablets

Drug: Placebo Oral Tablet

Rapamycin 1 mg/m2

ACTIVE COMPARATOR

Patients assigned to this arm will take Riluzole as usual + tablets corresponding to a Rapamycin dose of 1 mg/m2/day

Drug: Rapamycin; Drug: Placebo Oral Tablet

Rapamycin 2 mg/m2

ACTIVE COMPARATOR

Patients assigned to this arm will take Riluzole as usual + tablets corresponding to a Rapamycin dose of 2 mg/m2/day

Drug: Rapamycin

Interventions

Rapamycin DRUG

tablets containing Rapamycin/placebo will be administered based on body surface area and adjusted taking into consideration plasma rapamycin dosage

Also known as: Rapamune

Rapamycin 1 mg/m2; Rapamycin 2 mg/m2

Placebo Oral Tablet DRUG

tablets containing Rapamycin/placebo will be administered based on body surface area and adjusted taking into consideration plasma rapamycin dosage

Rapamycin 1 mg/m2; placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

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

Study Sites (7)

Centro Sla, Irccs A.O.U. S.Martino Ist, Genova

Genova, Italy

Location

Centro Clinico Nemo, Fondazione Serena Onlus, Milano

Milan, Italy

Location

Centro Sla, Irccs Istituto Carlo Besta, Milano

Milan, Italy

Location

Centro Sla, Ospedale Civile S. Agostino Estense, A.O.U. Modena

Modena, 41126, Italy

Location

Centro Sla, A.O.U. Maggiore Della Carita', Novara

Novara, Italy

Location

Centro Sla, Universita' Di Padova

Padua, Italy

Location

Centro Sla, Universita' Di Torino

Torino, Italy

Location

Related Publications (21)

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  PMID: 36008843 DERIVED

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis; Motor Neuron Disease

Interventions

Sirolimus

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; TDP-43 Proteinopathies; Neuromuscular Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Study Officials

• Jessica Mandrioli, MD

  Azienda Ospedaliero-Universitaria di Modena

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: treatment double blinded to patients and physicians
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, PI

Study Record Dates

• First Submitted: November 8, 2017
• First Posted: December 2, 2017
• Study Start: September 19, 2017
• Primary Completion: December 15, 2020
• Study Completion: February 15, 2022
• Last Updated: September 19, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (7)