Safety and Tolerability of Phenylbutyrate in Inclusion Body Myositis

Study Overview
=================
Brief Summary
-----------------
This is a pilot study (phase 1 clinical trial) to evaluate the safety and tolerability of phenylbutyrate in IBM. In this open label study, 10 patients with sporadic inclusion body myositis will be treated with phenylbutyrate (3 gm twice daily) for 3 months. There will be a run-in period, during which certain biomarkers will be measured at baseline and at the end of the run-in period in addition to final measurement at the end of the treatment period.

Official Title
-----------------
Safety and Tolerability of Phenylbutyrate in Inclusion Body Myositis

Conditions
-----------------
Inclusion Body Myositis, Sporadic Inclusion Body Myositis

Intervention / Treatment
-----------------
* Drug: Phenylbutyrate Oral Tablet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Fulfill ENMC 2011 diagnostic criteria for IBM Age > 18 years Women must be post-menopausal (no menses in >12 months) or status post hysterectomy Able to give informed consent Exclusion Criteria: Presence of any one of the following medical conditions: chronic infection; chronic renal insufficiency; cancer other than skin cancer less than five years prior; multiple sclerosis or prior episode of central nervous system demyelination; or other chronic serious medical illnesses Presence of any of the following on routine blood screening: WBC<3000; Platelets < 100,000; hematocrit < 30%; BUN > 30 mg %; creatine > 1.5 mg%; liver disease with serum albumin < 3 G/DL Women who are pregnant or lactating History of non-compliance with other therapies Coexistence of other muscular disease Drug or alcohol abuse within past three months Known bleeding disorder Known liver disease Known congestive heart failure Known hypernatremia Inability to give informed consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phenylbutyrate<br>Open-label phenylbutyrate | Drug: Phenylbutyrate Oral Tablet<br>* Phenylbutyrate, an orally active chemical chaperone approved by the US Food and Drug Administration for treatment of urea cycle disorders, mimics the function of intracellular molecular chaperones in preventing protein aggregation and oligomerization.<br>* Other names: PBA;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and Tolerability of Phenylbutyrate Measured by Incidence of Adverse Events | Since this is a Phase I pilot trial, the primary outcome will be testing the safety and tolerability of phenylbutyrate in patients with Inclusion Body Myositis. This will be measured by the incidence of adverse events reported in subjects throughout the treatment period of the trial. | Month 3 - Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Inclusion Body Myositis Functional Rating Scale (IBMFRS) | The IBMFRS is a quickly administered (10-minute) ordinal rating scale (ratings 0-40) used to determine patients' assessment of their capability and independence in 10 functional activities. The higher a subject scores on the scale, the better functional ability the subject has. | Month 6 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Inclusion Body Myositis, IBM, PBA, Phenylbutyrate