A Phase 2 interventional study of Rapamycin and Placebo Oral Tablet in Amyotrophic Lateral Sclerosis, sponsored by Azienda Ospedaliero-Universitaria di Modena. Completed at 7 sites in Italy. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2024-09-19.
Sponsored by Azienda Ospedaliero-Universitaria di Modena · Phase 2, Interventional, and Treatment
Among 89 studies in Amyotrophic Lateral Sclerosis with a site in Italy — 27 open to participants now, 36 under way, 7 of them phase 3. Amyotrophic Lateral Sclerosis · Italy.
Among the 89 studies in Amyotrophic Lateral Sclerosis with a site in Italy, this one is the 43rd largest by enrollment of the 69 interventional ones, is one of 6 that started in 2017, is one of 20 in phase 2, and was the 26th registered.
978 studies on the registry are indexed under Amyotrophic Lateral Sclerosis; 277 are open to participants now.
This study's enrollment of 63 is above the median of 38 across 662 interventional studies indexed under Amyotrophic Lateral Sclerosis.
Browse Amyotrophic Lateral Sclerosis studies →27 of the 89 studies in Amyotrophic Lateral Sclerosis with a site in Italy are open now, in 12 countries. Each count lists the studies.
Of the 192 Amyotrophic Lateral Sclerosis studies recruiting now, 117 (61%) set no upper age limit and 23 (12%) stop at 75 or younger; 15 take children under 18; 55 take healthy volunteers.
This study: 18 Years to 75 Years · all sexes · no healthy volunteers.
The full table on the hub →89 studies; the count open now beside each. This study's row is marked.
First in 2003; this study’s year is marked. 6 started in 2017.
Median enrollment 87 across the 69 interventional studies, 200 across the 20 observational. Of the 46 that completed or were terminated, 23 (50%) have results posted.
34 of 89 have an industry lead sponsor. The 10 most frequent:
Azienda Ospedaliero-Universitaria di Modena is the lead sponsor of 48 studies on the registry; 20 are open to participants now.
Azienda Ospedaliero-Universitaria di Modena has 4 studies filed under Amyotrophic Lateral Sclerosis — fewer than ten, so there is no comparison to draw.
11 of the studies in Amyotrophic Lateral Sclerosis with a site in Italy that are under way reach primary completion within a year, 2 of them phase 3. Phase 3 first, then by date:
| Study | Primary completion |
|---|---|
| NCT06126315Phase 3Mario Negri Institute for Pharmacological ResearchTrial on the Biological and Clinical Effects of Acetyl-L-carnitine in ALS | 2027-04 |
| NCT04856982Phase 3BiogenStudy to Learn If Tofersen (BIIB067) Can Delay ALS Symptoms and About Its Safety in Adults With a SOD1 Gene Mutation Who Have Not Yet Developed ALS Symptoms | 2027-08-07 |
| NCT06881979Istituti Clinici Scientifici Maugeri SpAHigh-Tech Rehabilitation Pathway for Chronic Adult Neuromuscular Diseases - Fit4MedRob-Chronic MND Project | 2026-11 |
| NCT07616050Marta MondelliniEvaluation of the Impact of Virtual Park on Training Motivation in Adult Patients | 2026-12 |
| NCT06318585Istituto Auxologico ItalianoCreation of a Clinical Database for the Study of Phenotypic Variability in Motor Neuron Diseases | 2026-12-31 |
Among the 89 studies in Amyotrophic Lateral Sclerosis with a site in Italy, from their registry updates:
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).
This is a phase II randomized, double-blind, placebo-controlled, multicenter clinical trial for people with ALS.
The aim is to study the biological and clinical effect of Rapamycin (in two different doses) in addition to Riluzole on ALS patients through comparison with patients treated with Riluzole and placebo.
Rapamycin has been shown to enhance proteins degradation, and this has been associated with beneficial effects in models of neurodegeneration. Its immunomodulatory effects are also well established, notably the ability to suppress inflammatory neurotoxic responses mediated by T cells. As ALS is characterized by heterogeneous pathology and protein accumulation, some patients may respond to therapies that accelerate the clearance of abnormally accumulated proteic aggregates, while suppressing neurotoxic immune elements.
Subjects will be enrolled in 3 groups of 21 subjects; treatment will be double blinded to patients and physicians, and will last 18 weeks. Active treatment will include oral Rapamycin at different doses: Rapamycin 1mg/m2/day or Rapamycin 2mg/m2/day. Rapamycin will be administered at fast, in the morning, once a day. Rapamycin levels will be measured (HPLC) to avoid toxicity (>15 ng/ml), but treating neurologists will have no access to blood laboratory data. Dosages will be adjusted accordingly and sham adjustments will be done in the placebo Group too. Post-treatment follow up will be 36 weeks. Globally the study will lasts 24 months. To monitor adverse events, examination and routine laboratory work (cell count, lipids and protein profile, kidney and liver function, C reactive protein) will be performed before taking Rapamycin/placebo. Non-routine laboratory studies include quantification and characterization of Tregs, lymphocytes phenotype, mTOR (mammilian target of rapamycin) downstream pathway activation in peripheral blood mononuclear cells (PBMC), inflammasome components in PBMC and proinflammatory cytokine production in monocytes, peripheral biomarkers. Cerebrospinal fluid (CSF) will be taken at baseline and at week 18 to measure neurofilaments and to dose Rapamycin to understand whether sufficient levels of Rapamycin can be found in the central nervous system (CNS).
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
BMI (body mass index)
Weight in kilograms divided by height in metres squared. Example: 70 kg and 1.75 m gives 70 ÷ (1.75 × 1.75) ≈ 22.9.
What counts as overweight or obesity differs between countries (some use lower cut-offs), so go by the range the study states.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Platelets
Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Patients assigned to this arm will take Riluzole as usual + placebo tablets
Drug: Placebo Oral Tablet
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
Patients assigned to this arm will take Riluzole as usual + tablets corresponding to a Rapamycin dose of 2 mg/m2/day
Drug: Rapamycin
tablets containing Rapamycin/placebo will be administered based on body surface area and adjusted taking into consideration plasma rapamycin dosage
Also known as: Rapamune
tablets containing Rapamycin/placebo will be administered based on body surface area and adjusted taking into consideration plasma rapamycin dosage
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
Time frame: comparison between baseline and treatment end (week 18)
Number of serious adverse events (SAEs) and AEs in placebo and treatment arms
Rapamycin safety and tolerability in a cohort of ALS patients
Time frame: At week 18 and 54
Rapamycin capacity to pass through blood brain barrier
HPLC-MS (mass spectrometry) dosage of Rapamycin in CSF in placebo and treatment arm will be performed at treatment end
Time frame: At week 18
Rapamycin efficacy in inhibiting Mtor pathway
Assessment of the phosphorylation of the S6 ribosomal protein (S6RP) comparing Rapamycin arms and placebo arm
Time frame: At week 8-18-30-54
Changes in activation and homing capabilities of different T, B, natural killer (NK) cell subpopulations
Change from baseline to each time point (week 8, 18, 30, and 54) of the activation and homing capabilities of different T, B, NK cell subpopulations comparing Rapamycin arms and placebo arm.
Time frame: At baseline and at week 8-18-30-54
Changes in CSF neurofilaments
Changes from baseline to week 18 of the levels of neurofilaments in CSF in treatment and placebo arms
Time frame: Baseline and week 18
Changes in blood biomarkers
Changes from baseline to week 8-18-30.54 of the levels of neurofilaments and vitamin D in treatment and placebo arms
Time frame: Baseline, week 8-18-30-54
Rapamycin-induced changes in inflammatory status
Changes from baseline to each time point (week 8, 18, 30, and 54) in inflammatory status (cytokines and cells) (molecular analysis of the inflammasome system) comparing Rapamycin arms and placebo arm
Time frame: Baseline and week 8-18-30-54
Changes in Amyotrophic Lateral Sclerosis functional rating scale (ALSFRS)-Revised
ALSFRS-R score changes from baseline to week 4, 8, 12, 18, 30, 42 and week 54 in treatment and placebo arms.
Time frame: Up to week 54
Tracheostomy-free survival rate
Overall survival from randomization to date of death or tracheostomy
Time frame: Up to week 54
Changes in Forced vital capacity (FVC)
Changes in FVC score from baseline to week 4, 8, 12, 18, 30, 42, 54 in treatment and placebo arms.
Time frame: Up to week 54
Change in quality of life
Changes in Amyotrophic Lateral Sclerosis Assessment Questionnaire (ALSAQ-40) from baseline to week 8, 18, 30 and week 54, in placebo and treatment arms
Time frame: From baseline to week 8, 18, 30 and week 54
Plan to share: No
Ran from Sep 2017 to primary completion in Dec 2020, 38 months.
Of 37 non-industry phase 2 interventional studies under Amyotrophic Lateral Sclerosis, half reached primary completion within 32 months of starting (the median), counting those still running; a quarter within 18 and three quarters within 41. This study's 38 months is above that.
Counting every sponsor, half of 73 studies reached it within 24 months; a quarter within 16 and three quarters within 35.
How these figures are worked out, and which studies are left out of them.
This study is completed, as verified in Sep 2024. You cannot join it, but the record below documents what was studied.
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Studies of the drug tested here: Sirolimus
Amyotrophic Lateral Sclerosis →
Azienda Ospedaliero-Universitaria di Modena