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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01676077




Registration number
NCT01676077
Ethics application status
Date submitted
28/08/2012
Date registered
30/08/2012
Date last updated
26/07/2022

Titles & IDs
Public title
Clinical Outcome Study for Dysferlinopathy
Scientific title
International Clinical Outcome Study for Dysferlinopathy
Secondary ID [1] 0 0
85750
Universal Trial Number (UTN)
Trial acronym
Jain COS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Dysferlinopathy 0 0
LGMD2B Now Classified as LGMDR2 0 0
Miyoshi Myopathy 0 0
Critically Ill Adults Ventilated >24 Hours in Intensive Care 0 0
COPD 0 0
Cancer 0 0
Condition category
Condition code
Musculoskeletal 0 0 0 0
Other muscular and skeletal disorders
Human Genetics and Inherited Disorders 0 0 0 0
Other human genetics and inherited disorders
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Observational
Patient registry
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Treatment: Other - Radiotherapy

Patients with a genetically confirmed dysferlinopathy -

Placebo comparator: Portable Oxygen Cylinder - Portable Oxygen Cylinder

Active comparator: Portable Oxygen Concentrator - Portable Oxygen Concentrator

Experimental: Radiotherapy - The interventional treatment will be prescribed as a 2-tiered dose scheduled dependant of target size.

For lesions \<5cm, a single fraction of 26 Gy will be prescribed. For lesions =5cm a fractionated course of 15Gy by 3 fractions will be prescribed, delivered at least 48 hours apart.


Treatment: Other: Radiotherapy
The investigational treatment will be prescribed as a 2-tiered dose scheduled dependant on target size.

For lesions \<5cm, a single fraction of 26Gy will be prescribed. For lesions =5cm a fractionated course of 14Gy by 3 fractions will be prescribed, delivered at least 48 hours apart.
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
VARC-2 Composite Safety Endpoint
Timepoint [1] 0 0
30 days
Primary outcome [2] 0 0
North Star assessment for limb girdle-type muscular dystrophies (NSAD)
Timepoint [2] 0 0
24 months
Primary outcome [3] 0 0
Best level of activity in ICU
Timepoint [3] 0 0
ICU stay (average 7 days)
Primary outcome [4] 0 0
Dosage of the best level of activity
Timepoint [4] 0 0
Intensive care unit stay (average 7 days)
Primary outcome [5] 0 0
Time to standing in ICU
Timepoint [5] 0 0
Intensive care stay (average 7 days)
Primary outcome [6] 0 0
Quality of life as measured through Chronic Respiratory Questionnaire
Timepoint [6] 0 0
One month
Primary outcome [7] 0 0
The number of patients who complete prescribed treatment.
Timepoint [7] 0 0
After 24 months
Secondary outcome [1] 0 0
All Cause Mortality
Timepoint [1] 0 0
30 days
Secondary outcome [2] 0 0
All Cause Mortality
Timepoint [2] 0 0
12 months
Secondary outcome [3] 0 0
Best level of activity at hospital discharge
Timepoint [3] 0 0
Hospital stay (median days 14)
Secondary outcome [4] 0 0
Time to first sit out of bed
Timepoint [4] 0 0
ICU stay (average 7 days)
Secondary outcome [5] 0 0
Barriers to mobilisation
Timepoint [5] 0 0
Intensive care unit stay (average 7 days)
Secondary outcome [6] 0 0
Mobilization related adverse events
Timepoint [6] 0 0
Intensive care unit stay (average 7 days)
Secondary outcome [7] 0 0
Time to first physiotherapy
Timepoint [7] 0 0
Intensive care unit stay (average 7 days)
Secondary outcome [8] 0 0
Mechanical ventilation free days
Timepoint [8] 0 0
28 days
Secondary outcome [9] 0 0
Intensive care unit free days
Timepoint [9] 0 0
Day 28
Secondary outcome [10] 0 0
90 day mortality
Timepoint [10] 0 0
90 days
Secondary outcome [11] 0 0
Health related quality of life at 6 months
Timepoint [11] 0 0
6 months
Secondary outcome [12] 0 0
Patient Preference
Timepoint [12] 0 0
One month
Secondary outcome [13] 0 0
Cost effectiveness of portable oxygen concentrator compared to cylinder
Timepoint [13] 0 0
one month
Secondary outcome [14] 0 0
Quality of life as measured through AQoL-8D
Timepoint [14] 0 0
One month
Secondary outcome [15] 0 0
Toxicity of SBRT in study patients measured using CTCAE V4.0
Timepoint [15] 0 0
Between 2-4 weeks after radiotherapy and 3 monthly for 12 months
Secondary outcome [16] 0 0
Efficacy of stereotactic radiosurgery
Timepoint [16] 0 0
1 year after treatment
Secondary outcome [17] 0 0
Feasibility of using Diffusion weighted-MRI for response assessment.
Timepoint [17] 0 0
At Baseline, 14 days (+/-3 days) and at the definitive response assessment (70days +/-10days)

Eligibility
Key inclusion criteria
- Confirmed diagnosis of dysferlinopathy proven by a) two (predicted) pathogenic dysferlin mutations, b) one (predicted) pathogenic dysferlin mutation and absent dysferlin protein on muscle immunoblot, or c) one (predicted) pathogenic dysferlin mutation and dysferlin protein level =20% of normal level determined by blood monocyte testing. Mutations will be checked for pathogenicity via the UMD bioinformatics tools and and by checking the literature and mutation /variant databases.

NOTE: Contact Sarah Shira at the Jain Foundation for help with diagnosis at +1 425 882 1492

* Ambulant with or without aids; or full-time wheelchair user, i.e. non-ambulant; with the ratio 2:1 between recruited ambulant and recruited non-ambulant patients.
* All ages = 10 years of age.
* Ability to perform assessments (there will be different assessments for ambulant and non-ambulant patients).
* Ability to attend scheduled investigations.
* Informed consent to participate in the clinical outcome study.

NOTE: Funds are available to cover necessary hotel stays and travel costs to the study centres for the participant and a helper (if needed).
Minimum age
10 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Known current or planned medical or other interventions that might interfere with the possibility to undertake the planned tests.
* Other concomitant pathology that in the view of the investigator would jeopardise the ability to take part in the protocol.

Study design
Purpose
Duration
Selection
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
UNKNOWN
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
1/09/2012
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/03/2024
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC,WA
Recruitment hospital [1] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 0 0
Macquarie Unversity Hospital - Macquarie Park
Recruitment hospital [3] 0 0
Prince of Wales Hospital - Randwick
Recruitment hospital [4] 0 0
Royal North Shore Hospital - St. Leonards
Recruitment hospital [5] 0 0
The Prince Charles Hospital - Chermside
Recruitment hospital [6] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [7] 0 0
Flinders Medical Centre - Bedford Park
Recruitment hospital [8] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [9] 0 0
St Vincent's Hospital - MELBOURNE - Melbourne
Recruitment hospital [10] 0 0
Royal Melbourne Hospital - Parkville
Recruitment hospital [11] 0 0
Royal Perth Hospital/Fiona Stanley Hospital - Perth
Recruitment hospital [12] 0 0
The Alfred - Melbourne
Recruitment hospital [13] 0 0
The Queen Elizabeth Hospital - Woodville Road, Woodville
Recruitment hospital [14] 0 0
Peter MacCallum Cancer Centre - East Melbourne
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2109 - Macquarie Park
Recruitment postcode(s) [3] 0 0
2031 - Randwick
Recruitment postcode(s) [4] 0 0
2065 - St. Leonards
Recruitment postcode(s) [5] 0 0
4032 - Chermside
Recruitment postcode(s) [6] 0 0
5000 - Adelaide
Recruitment postcode(s) [7] 0 0
5042 - Bedford Park
Recruitment postcode(s) [8] 0 0
3004 - Melbourne
Recruitment postcode(s) [9] 0 0
3065 - Melbourne
Recruitment postcode(s) [10] 0 0
3050 - Parkville
Recruitment postcode(s) [11] 0 0
6000 - Perth
Recruitment postcode(s) [12] 0 0
3104 - Melbourne
Recruitment postcode(s) [13] 0 0
5022 - Woodville Road, Woodville
Recruitment postcode(s) [14] 0 0
3002 - East Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Missouri
Country [3] 0 0
United States of America
State/province [3] 0 0
New York
Country [4] 0 0
United States of America
State/province [4] 0 0
North Carolina
Country [5] 0 0
United States of America
State/province [5] 0 0
Ohio
Country [6] 0 0
Chile
State/province [6] 0 0
Santiago
Country [7] 0 0
Denmark
State/province [7] 0 0
Copenhagen
Country [8] 0 0
France
State/province [8] 0 0
Paris
Country [9] 0 0
Italy
State/province [9] 0 0
Padova
Country [10] 0 0
Japan
State/province [10] 0 0
Tokyo
Country [11] 0 0
Korea, Republic of
State/province [11] 0 0
Busan
Country [12] 0 0
Spain
State/province [12] 0 0
Barcelona
Country [13] 0 0
Spain
State/province [13] 0 0
San Sebastián
Country [14] 0 0
Spain
State/province [14] 0 0
Sevilla
Country [15] 0 0
United Kingdom
State/province [15] 0 0
Newcastle upon Tyne
Country [16] 0 0
New Zealand
State/province [16] 0 0
Wellington

Funding & Sponsors
Primary sponsor type
Other
Name
Newcastle-upon-Tyne Hospitals NHS Trust
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Jain Foundation
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Pacific Clinical Research Group
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Intensive Care Foundation, Australia
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
The "Clinical Outcome Study for Dysferlinopathy" is being performed in centres in Europe (UK- Newcastle; Spain- Barcelona, Sevilla; San Sebastian;Denmark, Copenhagen, Italy- Padova; France- Paris,), USA (Charlotte, NC; Columbus, OH; St.Louis, MO, Stanford CA, Irvine CA and Columbia NY), Chile (Santiago) Japan (Tokyo) and South Korea (Pusan). Oversight is provided by Newcastle upon Tyne Hospitals Trust. Funding for this study is being provided by the Jain Foundation, a non-profit foundation dedicated to finding therapies for dysferlinopathies(LGMD2b/Miyoshi). The aim of this "Clinical Outcome Study" is to determine the clinical outcome measures required for future clinical trials, characterize the disease progression of dysferlinopathy and collect biological samples for the identification of disease markers that are needed to non-invasively monitor the disease during clinical trials. Without this information, effective clinical trials cannot be performed.

This study is recruiting a large number of genetically confirmed dysferlinopathy patients aged 10 years or older, who are ambulant or non-ambulant. The study has reopened for a further two years (COS2). Participants will be assessed at 4 further visits over 2 years via medical, physiotherapy, and MRI/MRS assessments, as well as standard blood tests. Optionally, the participants can donate blood samples and a skin sample for use in the identification of disease markers and other approved research. There is a sub-study running in MRI at selected sites.
Trial website
https://clinicaltrials.gov/study/NCT01676077
Trial related presentations / publications
Moore U, Jacobs M, James MK, Mayhew AG, Fernandez-Torron R, Feng J, Cnaan A, Eagle M, Bettinson K, Rufibach LE, Lofra RM, Blamire AM, Carlier PG, Mittal P, Lowes LP, Alfano L, Rose K, Duong T, Berry KM, Montiel-Morillo E, Pedrosa-Hernandez I, Holsten S, Sanjak M, Ashida A, Sakamoto C, Tateishi T, Yajima H, Canal A, Ollivier G, Decostre V, Mendez JB, Sanchez-Aguilera Praxedes N, Thiele S, Siener C, Shierbecker J, Florence JM, Vandevelde B, DeWolf B, Hutchence M, Gee R, Prugel J, Maron E, Hilsden H, Lochmuller H, Grieben U, Spuler S, Tesi Rocha C, Day JW, Jones KJ, Bharucha-Goebel DX, Salort-Campana E, Harms M, Pestronk A, Krause S, Schreiber-Katz O, Walter MC, Paradas C, Hogrel JY, Stojkovic T, Takeda S, Mori-Yoshimura M, Bravver E, Sparks S, Diaz-Manera J, Bello L, Semplicini C, Pegoraro E, Mendell JR, Bushby K, Straub V; Jain COS Consortium. Assessment of disease progression in dysferlinopathy: A 1-year cohort study. Neurology. 2019 Jan 28;92(5):e461-e474. doi: 10.1212/WNL.0000000000006858.
Diaz-Manera J, Fernandez-Torron R, LLauger J, James MK, Mayhew A, Smith FE, Moore UR, Blamire AM, Carlier PG, Rufibach L, Mittal P, Eagle M, Jacobs M, Hodgson T, Wallace D, Ward L, Smith M, Stramare R, Rampado A, Sato N, Tamaru T, Harwick B, Rico Gala S, Turk S, Coppenrath EM, Foster G, Bendahan D, Le Fur Y, Fricke ST, Otero H, Foster SL, Peduto A, Sawyer AM, Hilsden H, Lochmuller H, Grieben U, Spuler S, Tesi Rocha C, Day JW, Jones KJ, Bharucha-Goebel DX, Salort-Campana E, Harms M, Pestronk A, Krause S, Schreiber-Katz O, Walter MC, Paradas C, Hogrel JY, Stojkovic T, Takeda S, Mori-Yoshimura M, Bravver E, Sparks S, Bello L, Semplicini C, Pegoraro E, Mendell JR, Bushby K, Straub V; Jain COS Consortium. Muscle MRI in patients with dysferlinopathy: pattern recognition and implications for clinical trials. J Neurol Neurosurg Psychiatry. 2018 Oct;89(10):1071-1081. doi: 10.1136/jnnp-2017-317488. Epub 2018 May 7.
Moore UR, Jacobs M, Fernandez-Torron R, Jang J, James MK, Mayhew A, Rufibach L, Mittal P, Eagle M, Cnaan A, Carlier PG, Blamire A, Hilsden H, Lochmuller H, Grieben U, Spuler S, Tesi Rocha C, Day JW, Jones KJ, Bharucha-Goebel DX, Salort-Campana E, Harms M, Pestronk A, Krause S, Schreiber-Katz O, Walter MC, Paradas C, Hogrel JY, Stojkovic T, Takeda S, Mori-Yoshimura M, Bravver E, Sparks S, Diaz-Manera J, Bello L, Semplicini C, Pegoraro E, Mendell JR, Bushby K, Straub V. Teenage exercise is associated with earlier symptom onset in dysferlinopathy: a retrospective cohort study. J Neurol Neurosurg Psychiatry. 2018 Nov;89(11):1224-1226. doi: 10.1136/jnnp-2017-317329. Epub 2018 Jan 29. No abstract available.
TEAM Study Investigators; Hodgson C, Bellomo R, Berney S, Bailey M, Buhr H, Denehy L, Harrold M, Higgins A, Presneill J, Saxena M, Skinner E, Young P, Webb S. Early mobilization and recovery in mechanically ventilated patients in the ICU: a bi-national, multi-centre, prospective cohort study. Crit Care. 2015 Feb 26;19(1):81. doi: 10.1186/s13054-015-0765-4.
Tipping CJ, Bailey MJ, Bellomo R, Berney S, Buhr H, Denehy L, Harrold M, Holland A, Higgins AM, Iwashyna TJ, Needham D, Presneill J, Saxena M, Skinner EH, Webb S, Young P, Zanni J, Hodgson CL. The ICU Mobility Scale Has Construct and Predictive Validity and Is Responsive. A Multicenter Observational Study. Ann Am Thorac Soc. 2016 Jun;13(6):887-93. doi: 10.1513/AnnalsATS.201510-717OC.
Pham D, Thompson A, Kron T, Foroudi F, Kolsky MS, Devereux T, Lim A, Siva S. Stereotactic ablative body radiation therapy for primary kidney cancer: a 3-dimensional conformal technique associated with low rates of early toxicity. Int J Radiat Oncol Biol Phys. 2014 Dec 1;90(5):1061-8. doi: 10.1016/j.ijrobp.2014.07.043. Epub 2014 Oct 13.
Public notes

Contacts
Principal investigator
Name 0 0
Volker Straub
Address 0 0
Newcastle University
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT01676077