Clinical trial NCT03707795: Treatment of FUS-Related ALS With Betamethasone - The TRANSLATE Study
Official title: Treatment of FUS-Related ALS With Betamethasone - The TRANSLATE Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Familial Amyotrophic Lateral Sclerosis
Lead sponsor: University of Kentucky
Sponsor class: OTHER
First posted: 2018-10-16
Enrollment: 6
Sex: ALL
Minimum age (years): 20
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of familial ALS (fALS)
* Relative of a fALS person and carry the FUS gene

Exclusion Criteria:

* Under 20 years or over 80 years of age
* Cannot tolerate steroids, including betamethasone
* Are unwilling or unable to attend all scheduled research visits
* Currently participating in another clinical drug trial
* Major neurological disease, other than ALS
* Pregnant

Primary outcomes:
measure: Betamethasone plasma levels
timeFrame: 14 days
Secondary outcomes:
measure: Protein carbonyl plasma levels
timeFrame: 14 days
measure: Superoxide dismutase plasma levels
timeFrame: 14 days
measure: Peroxide plasma levels
timeFrame: 14 days
measure: Glutathione disulfide plasma levels
timeFrame: 14 days
measure: Glutathione plasma levels
timeFrame: 14 days
Other outcomes:
measure: Slow vital capacity
timeFrame: 14 days
measure: Maximum voluntary ventilation (MVV)
timeFrame: 14 days
measure: Grip strength
timeFrame: 14 days
measure: Manual dexterity
timeFrame: 14 days
measure: Sit to stand assessment
timeFrame: 14 days
measure: Time walk assessment
timeFrame: 14 days
measure: Isometric strength generation
timeFrame: 14 days
Locations:
city: Lexington
country: United States
facility: University of Kentucky Medical Center
state: Kentucky
Study officials:
affiliation: University of Kentucky
name: Edward Kasarskis, MD
role: PRINCIPAL_INVESTIGATOR
References: