Treatment of FUS-Related ALS With Betamethasone - The TRANSLATE Study
Condition: Familial Amyotrophic Lateral Sclerosis
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis
Study type: Interventional
Phase: Early Phase 1

Summary: 
      By doing this study the investigator hopes to learn more about a potential cause of
      amyotrophic lateral sclerosis (ALS) called "oxidative stress". Oxidative stress is
      essentially an imbalance between the production of certain chemicals in the body called "free
      radicals" and the ability of the body to counteract or detoxify their harmful effects through
      neutralization by antioxidants. It is thought that factors such as environmental exposure
      (chemicals and lead), diet, smoking,alcohol consumption, physical activity and psychological
      stress cause oxidative stress to occur inside the body.

      By doing this study, the investigator hopes to learn whether the FDA-approved steroid
      medication called Betamethasone will restore overall antioxidant activity fALS patients with
      mutations in the Fused in Sarcoma gene (FUS gene).

      Participants who agree to take part in this research study, agree to the following
      responsibilities:

        -  Attend all scheduled visits

        -  Notify the study doctor of any illnesses, unexpected or troublesome side effects, or any
           other medical problems that occur during the study

        -  Be completely honest with their answers to all questions

        -  Check with the study doctor before taking any new medications, whether prescribed or
           "over the counter," even vitamins and herbal supplements.
    

Detailed description: 
      This will be a single-blinded, pharmacokinetic and pharmacodynamics study of intramuscular
      (IM) betamethasone in ALS patients and non-ALS relatives from families with a mutation in the
      FUS gene. Participants remain blinded as to their genotype.

      Betamethasone is a FDA-approved drug and is only available in an IM dosing form (Celestone®).
      This will be a proof-of-concept translational study built on discoveries made by our research
      team at the University of Kentucky. All participants will receive active drug.

      The research procedures will be conducted at the University of Kentucky (UK) Albert B.
      Chandler Hospital, Pavilion H, 800 Rose Street, Lexington, KY. Participants will need to come
      to Center for Clinical and Translational Science (CCTS) on the 3rd Floor (Room C300) of
      Pavilion H, at UK Albert B. Chandler Hospital, for a Consent/Screening Visit. If found
      eligible and qualify for the study, participants will be asked to give voluntary written
      consent to participate.

      Following signing the consent form, participants will be admitted to the UK Albert B.
      Chandler Hospital, CCTS Inpatient Unit, 5th Floor, 5 North Wing of the Hospital for 2 nights
      (approximately 48 hours). The following tests and procedures will take place:

        -  Neurological Exam

        -  Vital Signs (blood pressure, heart rate and respiratory rate) will be measured

        -  Medical and medication history will be collected

        -  Questionnaire

        -  blood specimen for Pharmacokinetic and Pharmacodynamic will be collected testing*

        -  Participants will also be asked to do some testing of their breathing and physical
           abilities.

      The study drug (betamethasone sodium phosphate/betamethasone acetate [Celestone® Soluspan®])
      will be injected into a muscle such as arm or buttock - this will be the first of the four
      injections of the study drug administered during the study.

      At 24 hours after the first injection with the study drug, and while still in the the
      hospital, the study drug will again be injected into a muscle such as arm or buttock - this
      will be the second of the four injections of the study drug administered during the study.

      Following this second treatment, and after the study doctor determines it is safe, the
      participant will be discharged from the hospital. They will will stay in a local motel
      overnight, awaiting the next day's blood draw, assessments, testing and 3rd treatment with
      study drug.

      Participants who do not live close to the hospital, motel accommodations will be provided at
      no charge, for an overnight stay between the 48 Hour visit, and the 72 Hour scheduled
      follow-up visit.

      At 72 hours after first injection with the study drug, the study drug will again be injected
      into a muscle such as arm or buttock - this will be the fourth and last of the four
      injections administered during the study. Following this fourth treatment, and after the
      study doctor determines if is safe, participants will be allowed to leave.

      The 72 Hour (Day 3), 168 Hour (Day 7) and 336 Hour (Day 14) visits will take about 1 hour
      each. The approximate, total amount of time participants will be asked to volunteer for this
      study is 51 hours over the 336 hour (14 day) duration of this research study.

      Participants or their insurance company, Medicare or Medicaid will be responsible for the
      costs of all routine medical care and treatment they would normally receive for their
      condition. The University of Kentucky may not be allowed to bill insurance companies,
      Medicare or Medicaid for the medical procedures done strictly for research.

      Neither the participant or their provider will be charged for costs of any of the procedures
      performed for the research study.
    

Intervention name(s): Betamethasone sodium phosphate/betamethasone acetate (Celestone® Soluspan®), 30 mg IM once a day for four days
Intervention type(s): Drug
Intervention description(s): Participants will be given four IM injections throughout the study
Intervention MeSH terms: Betamethasone; Betamethasone Valerate; Betamethasone-17,21-dipropionate; Betamethasone benzoate; Betamethasone acetate; Betamethasone acetate phosphate; Betamethasone sodium phosphate
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: Single (Participant)
Primary purpose: Treatment