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Neurovascular/Stroke Clinical Trials

Phase II/III Randomized, Placebo-controlled Trial of Arimoclomol in SOD1 Positive Familial Amyotrophic Lateral Sclerosis

NCT ID: NCT00706147
Principal Investigator: Michael Benatar, MBChB, DPhil

The purpose of this study will be to demonstrate the safety, tolerability, and efficacy of arimoclomol in subjects with SOD1 positive familial Amyotrophic Lateral Sclerosis (ALS). This type of ALS is HEREDITARY (runs in families), and at least one other person in the family must have had ALS. Study hypotheses: Arimoclomol, taken at a dose of 200 mg three times daily will improve survival as defined by time to death, tracheostomy or permanent assisted ventilation. In addition, it will be safe and well tolerated in subjects with SOD1 positive familial ALS. Funding Source - FDA-OOPD

Condition:

Using a seamless, adaptive, phase II/III design, the investigators will determine the safety and efficacy of arimoclomol in patients with SOD1 positive familial ALS. Both stage-1 and stage-2 are randomized, double-blind and placebo-controlled in a population of patients with rapidly progressive SOD1 positive familial ALS. Patients with ALS, a history of a relative affected with ALS (i.e. familial ALS) and the presence of a demonstrable mutation in the SOD1 gene that is known to be associated with rapidly progressive disease, will be eligible for inclusion in this study. Potentially eligible subjects will undergo screening via telephone and, if necessary, review of outside medical records. The intervention will continue for up to 12 months. In the event that a participant reaches a study endpoint (e.g. tracheostomy or permanently assisted ventilation) study drug will be terminated. Subjects who meet all eligibility criteria will travel a study site for final eligibility determination, baseline evaluation and will then be randomized 1:1 to receive either placebo or arimoclomol at a dose of 200 mg t.i.d. Participants will then be evaluated again in person at a study site at Month-2. Subsequent telephonic evaluations at Month-3, -4, -5, -6, -8, and -10 will be performed in participants' homes. Safety and tolerability evaluations will be performed at each of these visits. Collection of blood samples for safety laboratory analyses and measurement of blood pressure, heart rate, respiratory rate, temperature and weight will be performed at Months -1, -3, -5, -6, -8, and -10 in the participant's home by a representative of a medical monitoring company. A study coordinator may perform an in-person visit at Month-12, or this visit may occur telephonically. A final evaluation will be performed via telephone at Month -13 (30 days after the last dose of study medication).

Eligibility:

Inclusion Criteria: - Type of ALS that is hereditary (runs in families) only. - El Escorial criteria for familial ALS and a family history of a pathogenic mutation in a gene known to be associated with ALS, such as the SOD1 gene. - Willingness to undergo genetic testing and to learn the results. - Demonstrable mutation in the SOD1 gene that is reported to be associated with a rapid rate of disease progression (i.e. A4V, A4T, C6F, C6G, V7E, L8Q, G10V, G41S, H43R, H48Q, D90V, G93A, D101H, D101Y, L106V, I112M, I112T, R115G, L126X, G127X, A145T, V148G, V148I) or possibly associated with rapidly progressive disease (E21G, G37R, L38V, D76Y, L84F, L84V, N86S, D90A het, G93R, I104F, I113T, L144F, L144S). - Age 18 years or older; male or female. - Capable of providing informed consent and complying with trial procedures. - Diagnosis within less than 9 months of the anticipated date of the baseline visit AND study participants' subjective evaluation that they expect their physical condition to permit travel to the study site for both the baseline and 2-month study visits. - Women must not be able to become pregnant (e.g. post menopausal for at least one year, surgically sterile, or practicing adequate birth control methods) for the duration of the study. Adequate contraception includes: oral contraception, implanted contraception, intrauterine device in place for at least 3 months, or barrier method in conjunction with spermicide. - Women of childbearing potential must have a negative pregnancy test at screening visit and be non-lactating. - Willing to remain on a stable dose of Riluzole or to remain off Riluzole for the duration of the trial. - Identifiable local medical doctor to assist with urgent care of any medical complications that may arise. - Absence of any of the exclusion criteria. Exclusion Criteria: - History of known sensitivity or intolerability to Arimoclomol or to any other related compound. - Exposure to any investigational drug within 30 days of the screening visit. - Presence of any of the following clinical conditions: - Substance abuse within the past year. - Unstable cardiac, pulmonary, renal, hepatic, endocrine, hematologic, or active infectious disease. - AIDS or AIDS-related complex. - Unstable psychiatric illness defined as psychosis (hallucinations or delusions), untreated major depression within 90 days of the screening visit. - Positive pregnancy test at screening visit. - Screening laboratory values: - Creatinine greater than 1.5. - Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST). greater than 3.0 times the upper limit of normal. - Total bilirubin greater than 2.0 times the upper limit of normal. - White blood cell (WBC) count less than 3,500/mm3. - Platelet concentration less than 100,000/ul. - Hematocrit level less than 33 for female or less than 35 for male. - Female patients who are breast-feeding.

Gender: Both
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No

Clinical Trial Ceftriaxone in Subjects With ALS

NCT ID: NCT00349622
Principal Investigator: Merit Cudkowicz, MD, MSc.

The purpose of the study is to evaluate the safety and efficacy of ceftriaxone treatment in amyotrophic lateral sclerosis (ALS).

Condition:

It is known that nerve cells called motor neurons die in the brains and spinal cords of people with amyotrophic lateral sclerosis (ALS). However, the cause of this cell death is unknown. Researchers think that increased levels of a chemical called "glutamate" may be related to the cell death. For this reason researchers want to study drugs that decrease glutamate levels near nerves. Ceftriaxone—a semi-synthetic, third generation cephalosporin antibiotic—may increase the level of a protein that decreases glutamate levels near nerves. Studies of ceftriaxone in the laboratory suggest that it may protect motor neurons from injury. Ceftriaxone is approved by the U.S. Food and Drug Administration (FDA) for treating bacterial infections but not for treating ALS. Also, ceftriaxone has not been given to people over a long period of time, such as months or years. The goals of this study are to evaluate the safety and effectiveness of ceftriaxone as a treatment for ALS, and to determine the safety and effectiveness of long-term use of the drug in people with ALS. A total of 600 eligible people with ALS will be enrolled in this multi-center research study. Participants will be randomly assigned to receive treatment with ceftriaxone (2/3 of participants) or placebo (1/3 of participants) for at least 12 months. The study consists of three stages. The first stage, which has completed enrollment, will look at whether ceftriaxone enters the cerebrospinal fluid (the fluid that surrounds the spinal cord, also called CSF) in amounts that are high enough to be of possible benefit. The second stage, which has also completed enrollment, will look at the safety and side effects of the study drug when taken daily for at least 20 weeks. The study is currently enrolling subjects for the third stage, which began in Spring 2009, and will determine whether the study drug prolongs survival and slows decline in function due to ALS.

Eligibility:

Inclusion Criteria: - Participants will be people with ALS, at least 18 years of age. - Participants must be medically able to undergo the study procedures and have a caregiver or other individual who will be available to help with daily study medication administration. - Participants should live within a reasonable distance of the study site, due to frequent study visits. Exclusion Criteria: - Participants cannot be taking any other experimental medications for ALS, or have a history of sensitivity to cephalosporin antibiotics (such as Ancef, Keflex, Ceclor, Ceftin, Lorabid, Suprax, or Fortaz).

Gender: Both
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No

The Pre-symptomatic Familial Amyotrophic Lateral Sclerosis (Pre-fALS) Study

NCT ID: NCT00317616
Principal Investigator: Michael G Benatar, MD, PhD.
Contact: Eliana M Reyes, 1-888-413-9315

The investigators aim to recruit unaffected (healthy) people from families with a known genetic mutation in which at least two relatives have been affected with Amyotrophic Lateral Sclerosis (ALS). Our goal is to identify factors, both genetic and environmental, which put people at risk for developing ALS in the future.

Condition:

Healthy people from familial ALS families with a known genetic mutation will be included in this study. The investigators encourage people who know that they carry the mutation that affects their family as well as those who do not know their genetic status to contact us. Those who wish to participate and to learn the results of genetic testing, may do so after undergoing genetic counseling. It is also possible to participate without learning the results of genetic testing. Participants in the study will travel to Miami (at our expense) approximately every 12-24 months to complete study visits.

Eligibility:

Inclusion Criteria - A member of a family in which a mutation in a gene associated with ALS has been identified. This may include a family in which at least two relatives have been or currently are affected with ALS. - No symptoms to suggest the presence of ALS (i.e. study participants must currently be healthy). - Having at least 50% probability of carrying an ALS associated gene mutation. - Willingness to undergo genetic testing, with the option of whether or not to learn the results. - Willingness to travel to Miami approximately every 12 to 24 months for in-person study evaluations. Exclusion Criteria - Diagnosis of ALS - Any condition or situation which, in the PI's opinion, could confound the biomarker data or may interfere with the individual's participation and compliance with the study protocol, including but not limited to neurological, psychological and/or medical conditions.

Gender: Both
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No

Efficacy of Prednisone In the Treatment of Ocular Myasthenia

NCT ID: NCT00995722
Principal Investigator: Michael Benatar, MBChB, DPhil

The purpose of this study is to evaluate the efficacy and tolerability of prednisone in patients diagnosed with ocular myasthenia. Funding Source - FDA OOPD

Condition:

The purpose of this study is to learn two things about prednisone in patients with ocular myasthenia. The first thing we aim to learn is whether or not prednisone is effective in improving the symptoms of double vision and drooping eyes that are experienced by patients with ocular myasthenia. The second thing we aim to learn is whether we can find a dose of prednisone that is well tolerated and safe. The overall goal is to find out whether a dose of prednisone that is safe and well tolerated is also effective in improving the symptoms of ocular myasthenia. After completing screening assessments to confirm eligibility, all participants will receive treatment with pyridostigmine. If a participant's symptoms do not resolve within the first month while being treated with pyridostigmine, they will be randomized to receive prednisone or placebo. The amount of study medication a participant receives will depend on how their symptoms respond to the medication and if they experience any side effects. After four months, participants that continue to have symptoms of ocular myasthenia and do not have side effects will receive open label high dose prednisone. Participants that no longer have symptoms will taper their dose of study drug in a double-blind fashion.

Eligibility:

Inclusion Criteria: - Weakness confined to the extra-ocular muscles, eyelid levator and eye closure with an ocular-QMG1 score ≥ 1 - At least one of the following combinations of abnormal diagnostic testing: a) Elevated acetylcholine receptor antibody titers, (b) Abnormal repetitive nerve stimulation (> 10% decrement following slow repetitive nerve stimulation) of any nerve-muscle pair, (c) Abnormal jitter on single fiber or concentric needle electromyography in any muscle, (d) Positive ice test and brain MRI that demonstrates no central nervous system pathology that mimics ocular myasthenia, or (e) Positive Tensilon test and brain MRI that demonstrate no central nervous system pathology that mimics ocular myasthenia - Either no prior treatment with pyridostigmine, or participant has persistent ocular symptoms that are functionally limiting or troublesome despite treatment with pyridostigmine. - Age 18 years or older, male or female - Capable of providing informed consent and complying with study procedures - Identifiable primary care physician to assist with management of medical complications that may arise as a consequence of steroid therapy - Willing to be randomized to a trial of prednisone or placebo if symptoms respond inadequately to pyridostigmine. Exclusion Criteria: - Disease duration (time since symptom onset) > 5 years - Treatment with prednisone or other corticosteroids within 90 days of randomization - Treatment with azathioprine, cyclosporine, mycophenolate mofetil or other immune suppressive medication since onset of MG unless dosages of these medications and/or duration of therapy with these medications are clinically insignificant in the judgment of the PI - Intravenous immunoglobulin or plasma exchange within 90 days of randomization - Prior thymectomy or history of thymoma - Contraindication to steroids (poorly controlled diabetes, glaucoma or hypertension, history of prior steroid intolerance, obesity [BMI > 39.9kg/m2] or a history of osteoporotic fracture) - Pregnant or lactating - Renal failure, active thyroid or hepatocellular disease, chronic infection, poorly controlled cardiac disease, unstable psychiatric illness, untreated major depression or any other illness that would, in the opinion of the treating neurologist, make it unsafe for the patient to participate in the trial - Receipt of another investigational drug within 30 days of Screening

Gender: Both
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No

High Fat/High Calorie Trial in Amyotrophic Lateral Sclerosis

NCT ID: NCT00983983
Principal Investigator: Anne-Marie A Wills, M.D.

The purpose of this study is to determine the safety, tolerability, and preliminary efficacy of long-term use of high fat/high calorie and high calorie diets in people with amyotrophic lateral sclerosis (ALS) (Lou Gehrig's disease).

Condition:

Weight loss is a common and severe symptom of amyotrophic lateral sclerosis (ALS), caused both from inadequate calorie intake and an increased metabolic rate. People with ALS are generally instructed to increase their calorie intake; however, the ideal amount and type of calories has not been studied. Several studies in an animal model of motor neuron disease have shown that a high fat/high calorie diet can increase survival by as much as 38%. Mice on a high fat diet also live longer than mice fed diets consisting of high protein or high sugar. We are therefore conducting a phase II safety, tolerability, and preliminary efficacy trial in ALS of high fat versus high calorie versus normal diet. The normal diet will be calculated based on the number of calories needed to replace each participant's measured daily calorie requirement.

Eligibility:

Inclusion Criteria: 1. Clinical diagnosis of ALS 2. Male or female subjects aged 18 years or older 3. Must already be tolerating tube feedings through either a gastrostomy tube (G-tube or PEG) or jejunostomy tube (J-tube) 4. Must require non-invasive ventilation (BIPAP) for less than 10 hours/day 5. Women of childbearing potential must have a negative pregnancy test at screening and be non-lactating. Exclusion Criteria: 1. History of hepatitis including non-alcoholic steatohepatitis (NASH), cholecystectomy, prior biliary disease such as gallstones 2. History of diabetes 3. History of prior myocardial infarction or stroke 4. Laboratory values: Screening alanine aminotransferase (ALT) or aspartate aminotransferase (AST) greater than 2.0 times the upper limit of normal or total bilirubin greater than 1.5 times the upper limit of normal 5. Allergy to soy, fish, or milk products

Gender: Both
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No

Efficacy of Methotrexate in Myasthenia Gravis

NCT ID: NCT00814138
Principal Investigator: Richard Barohn, MD

Myasthenia gravis is a rare neuromuscular disorder characterized by weakness and fatigability of ocular, bulbar, and extremity musculature. The specific aim of this study is to determine if oral methotrexate is an effective therapy for myasthenia gravis (MG) patients who are prednisone dependent. Patients will be randomized to receive either methotrexate or placebo and those who are entered onto this trial will have symptoms and signs of the disease while on prednisone therapy. The hypothesis is that adding methotrexate therapy in these patients will improve the MG manifestations so that the prednisone dose can be reduced and clinical measures of MG severity will improve. Funding Source - FDA OOPD

Condition:

Eligibility:

Inclusion Criteria: - Patients must have MGFA MG grades 2, 3, or 4 generalized myasthenia gravis, according to the MGFA classification system - Elevated acetylcholine receptor antibody (AChR-Ab) titer. - Patient's signs and symptoms should not be better explained by another disease process. - Prednisone dose of at least 10 mg/day (or the equivalent in alternate days) and the subject must be on a stable dose of prednisone for 30 days prior to the screening visit. Exclusion Criteria: - A history of chronic degenerative, psychiatric, or neurologic disorder other than MG that can produce weakness or fatigue. - Other major chronic or debilitating illnesses within six months prior to study entry. - Female patients who are premenopausal and are: (a) pregnant on the basis of a serum pregnancy test, (b) breast-feeding, or (c) not using an effective method of double barrier (1 hormonal plus 1 barrier method or 2 simultaneous barrier methods) birth control (birth control pills, male condom, female condom, intrauterine device, Norplant, tubal ligation, or other sterilization procedures). - Altered levels of consciousness, dementia, or abnormal mental status. - Evidence of thymoma on chest CT or MRI. Such a finding could require immediate thymectomy and would preclude entry into the study. - Thymectomy in the previous three months. - Patients who have been medicated with azathioprine, cyclosporine, cyclophosphamide, mycophenolate mofetil, IVIg, or other immunosuppressive drugs within the last 60 days. - Chest X-ray with evidence of tumor, infection, or interstitial lung disease. - Clinical history of chronic or recurrent infections. - Daily use of non-steroidal anti-inflammatory drugs (NSAIDs). - History of renal or hepatic insufficiency or liver enzymes greater than the upper limit of normal. - History of bone marrow hypoplasia, leucopenia, thrombocytopenia, significant anemia, clinical or laboratory evidence of immunodeficiency syndromes. - Forced Vital Capacity (FVC) <50% of predicted. - MG Grade 1 (ocular only) or 5 (crisis, requiring ventilator). - Prior use of methotrexate for any condition.

Gender: Both
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No

A Study of NP001 in Subjects With Amyotrophic Lateral Sclerosis (ALS)

NCT ID: NCT01281631
Principal Investigator: Robert G. Miller, MD

This is a Phase 2 randomized, double-blind, placebo-controlled, multicenter study of NP001 in subjects with ALS.

Condition:

This is a randomized, double-blind, placebo-controlled study of NP001 in subjects with ALS conducted in multiple centers. Drug or placebo will be given intravenously. Approximately 105 subjects will be enrolled. Subjects will be allocated (1:1:1) to placebo and 2 dose levels of NP001.

Eligibility:

Subjects with sporadic or familial ALS classified as definite, probable, or laboratory-supported probable ALS according to the revised El Escorial criteria. A list of key criteria is listed below: Inclusion Criteria: - Onset of symptoms less than 3 years prior to study entry. - Forced Vital Capacity (FVC) at least 70% of that predicted for age and height. - Stable dose of riluzole if undergoing treatment with this agent. - For females: Not be of childbearing potential or agree to use adequate birth control during the study. Exclusion Criteria: - Unstable medical condition(s) other than ALS. - Life expectancy of less than 6 months. - Require life-sustaining interventions for the 6 months following randomization. - Have a tracheotomy or be using ventilatory assistance [including Bi-level Positive Airway Pressure (BiPAP) or Continuous Positive Airway Pressure (CPAP)]. - Active pulmonary disease. - Immune modulator therapy within 12 weeks of study entry or participation in studies of other agents within the last 4 weeks prior to the randomization.

Gender: Both
Minimum Age: 21 Years
Maximum Age: 80 Years
Healthy Volunteers: No

A Longitudinal Study of Amyotrophic Lateral Sclerosis (ALS) Biomarkers

NCT ID: NCT01495390
Contact: Sarah Titus, MPH, 617-726-1398

The purpose of this study is to collect biofluid samples for the banking and usage in ALS research. Through comparison of these samples, the researchers hope to learn more about the underlying cause of ALS, as well as find unique biological markers, which could be used to develop new therapies.

Condition:

The purpose of the research study is to collect blood samples and cerebrospinal fluid (CSF) from people with amyotrophic lateral sclerosis (ALS). These samples will be collected approximately every 4 months.

Eligibility:

Inclusion Criteria: - Age 18 or older - Diagnosis of suspected, possible, probable or definite ALS according to El Escorial Criteria - Vital capacity (VC) at least 50 percent predicted - Able to undergo multiple lumbar punctures Exclusion Criteria: - Abnormal CSF pressure or intracranial/intraspinal tumors - Use of anticoagulant medication that cannot be safely withheld - Bleeding disorders - This is a partial listing.

Gender: Both
Minimum Age: 18 Years
Maximum Age: N/A
Healthy Volunteers: No

A Study of NP001 in Subjects With Amyotrophic Lateral Sclerosis (ALS)

NCT ID: NCT01281631
Principal Investigator: Robert G. Miller, MD

This is a Phase 2 randomized, double-blind, placebo-controlled, multicenter study of NP001 in subjects with ALS.

Condition:

This is a randomized, double-blind, placebo-controlled study of NP001 in subjects with ALS conducted in multiple centers. Drug or placebo will be given intravenously. Approximately 105 subjects will be enrolled. Subjects will be allocated (1:1:1) to placebo and 2 dose levels of NP001.

Eligibility:

Subjects with sporadic or familial ALS classified as definite, probable, or laboratory-supported probable ALS according to the revised El Escorial criteria. A list of key criteria is listed below: Inclusion Criteria: - Onset of symptoms less than 3 years prior to study entry. - Forced Vital Capacity (FVC) at least 70% of that predicted for age and height. - Stable dose of riluzole if undergoing treatment with this agent. - For females: Not be of childbearing potential or agree to use adequate birth control during the study. Exclusion Criteria: - Unstable medical condition(s) other than ALS. - Life expectancy of less than 6 months. - Require life-sustaining interventions for the 6 months following randomization. - Have a tracheotomy or be using ventilatory assistance [including Bi-level Positive Airway Pressure (BiPAP) or Continuous Positive Airway Pressure (CPAP)]. - Active pulmonary disease. - Immune modulator therapy within 12 weeks of study entry or participation in studies of other agents within the last 4 weeks prior to the randomization.

Gender: Both
Minimum Age: 21 Years
Maximum Age: 80 Years
Healthy Volunteers: No