Clinical trial: Inhibition of Rho Kinase (ROCK) With Fasudil as Disease-modifying Treatment for ALS (NCT03792490)

Eligibility criteria:
Inclusion Criteria:

          -  Probable (clinically or laboratory) or definite ALS according to the revised version
             of the El Escorial World Federation of Neurology criteria

          -  Disease duration more than 6 months and less than 24 months (inclusive). Disease onset
             defined as date of first muscle weakness, excluding fasciculations and cramps

          -  Vital capacity more than 65% of normal (slow vital capacity; best of three
             measurements)

          -  Age: ≥ 18 years

          -  Patients have to be treated with Riluzole (2 x 50mg/d), must be stable for at least
             four weeks before randomization

          -  Patients who have started on Edaravone therapy shall continue Edaravone treatment.
             Edaravone treatment must not be discontinued for reasons of trial participation.

          -  Women of childbearing age must be non-lactating and surgically sterile or using a
             highly effective method of birth control and have a negative pregnancy test.
             Acceptable methods of birth control with a low failure rate i.e. less than 1% per
             year) when used consistently and correct are such as implants, injectables, combined
             oral contraceptives, hormonal intrauterine devices (IUDs), sexual abstinence or
             vasectomized partner

          -  Capable of thoroughly understanding all information given and giving full informed
             consent according to good clinical practice (GCP)

          -  Patients have to have a valid health insurance, when recruited in a center in France

        Exclusion Criteria:

          -  Previous participation in another clinical study involving trial medication within the
             preceding 12 weeks or five terminal half times of the longest to be eliminated trial
             medications (whichever is longer) or previous participation in this trial

          -  Tracheostomy or continuous assisted ventilation of any type during the preceding three
             months before randomization or a significant pulmonary disorder not attributed to ALS,
             which may complicate the evaluation of respiratory function, intermittent non-invasive
             ventilation is permitted,

          -  Patients with a history of intracranial bleeding, known intracerebral aneurysms or
             Moyamoya disease, or positive family history for the above. If only family history
             positive, magnetic resonance (MR)- or x-ray-based cranial imaging not older than 24
             months must confirm absence of bleeding, aneurysms or Moyamoya.

          -  Gastrostomy

          -  Any medical condition known to have an association with motor neuron dysfunction or
             involving neuromuscular weakness or another neurodegenerative disease, e.g.
             Parkinson's disease (PD) or Alzheimer's disease (AD), which might confound or obscure
             the diagnosis of ALS

          -  Presence of any concomitant life-threatening disease or impairment likely to interfere
             with functional assessment

          -  Patients with known arterial hypotension (resting blood pressure <90/60 mmHg) or
             previous hypotensive episodes or requiring treatment for increasing of blood pressure,
             such as fludrocortisone, midodrine, etilefrine, cafedrine or theodrenaline

          -  Patients with an uncontrollable or unstable arterial hypertensive disease (resting
             blood pressure >180 mmHg systolic and/or >120 mmHg diastolic under current
             antihypertensive medication)

          -  Known pulmonary hypertension and any medication prescribed for treatment of pulmonary
             hypertension

          -  Confirmed hepatic insufficiency or abnormal liver function (stable aspartate
             transaminase (ASAT) and/or alanine aminotransferase (ALAT) greater than 3 times the
             upper limit of the normal range) and determined to be non-transient through repeat
             testing

          -  Renal insufficiency with a glomerular filtration rate (GFR) <60 ml/min/1,73m²
             (calculated by Modification of Diet in Renal Disease (MDRD) equation) and determined
             to be non-transient through repeat testing

          -  Major psychiatric disorder, significant cognitive impairment or clinically evident
             dementia precluding evaluation of symptoms

          -  Hypersensitivity to any component of the study drug

          -  Liable to be not cooperative or comply with the trial requirements (as assessed by the
             investigator), or unable to be reached in the case of emergency

          -  Pregnant or breast-feeding females or females with childbearing potential, if no
             adequate contraceptive measures are used

          -  Prisoners or subjects who are involuntary incarcerated

          -  Patients subject to legal protection measures
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 18 Years old.


Patient description (medical language): A 47-year-old man comes to the clinic for the follow up of his neuromuscular disease. He experienced gradual, progressive weakness of the left upper extremity over the last year.  Over the last few months, he has also noticed weakness in the right upper extremity.  BP is 120/75, PR is 80 and temperature is 37 C. Reflexes are brisk in the upper extremities, and the plantar responses are extensor.  Mild gait ataxia is present. The patient is under treatment of Riluzole 50 mg BID with the diagnosis of ALS.

Patient description (patient's own words): I've been suffering from a neuromuscular disease for a while now, and I went to my doctor's office. I'm now a 47-year-old man and over the past year I experienced a progressive and gradual weakness of my left upper extremity, and over the past month, I also noticed a weakness over my right upper extremity. My heart rate was 120/75, and my  PR was 80 with 37°C for temperature. My reflexes are not good in my upper extremities, and I have trouble with my balance. I'm also under Exservan 50 mg for my sclerosis.

Does the patient match the trial criteria? Entailment