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Trial registered on ANZCTR


Registration number
ACTRN12615001260516
Ethics application status
Approved
Date submitted
15/11/2015
Date registered
18/11/2015
Date last updated
6/11/2019
Date data sharing statement initially provided
6/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety and efficacy of stem cell treatment for chronic migraine headache
Scientific title
A randomised, placebo-controlled, double-blind, proof of concept study of the safety and efficacy of autologous stromal vascular fraction (SVF) cells, in patients with moderate to severe chronic migraine headache
Secondary ID [1] 287571 0
Nil
Universal Trial Number (UTN)
U1111-1175-0069
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic migraine 296357 0
Condition category
Condition code
Neurological 296631 296631 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The primary objective of this study is to determine the safety and tolerability of stromal vascular fraction (SVF) compared to placebo in patients with chronic migraine headaches. The secondary objective is to measure differences between placebo and SVF.

Thirty participants will be enrolled in the study and randomly separated into 2 study groups.

Cohort 1: 15 patients administered with SVF (Day 0 and Day 30)

Cohort 2: 15 patients administered with placebo (Normal Saline; Day 0 and Day 30)

Autologous non-expanded SVF from adipose (fat) will be used due to the ease of harvest and safety (liposuction; about 60 min). The procedure will be performed by the Principle Investigator (Dr Ralph Bright - Physician and Cosmetic Surgeon), with the fat taken from the abdomen.

Cohort 1: [study drug] will have a SVF intravenous (IV) infusion of 3 million cells/kg of body weight in 500ml of Normal Saline after undergoing liposuction for 200 - 300 ml of adipose tissue (excess SVF will be cryo-preserved for the repeat treatment at Day 30).

The fat is processed on-site to isolate the cells (this process takes up to 40 mins approximately), and an infusion of SVF occurs immediately once the fat processing has finished.

Cohort 2: [placebo] will have an intravenous (IV) infusion of 500ml of Normal Saline (placebo), packaged in the same way as SVF after undergoing liposuction for 200 - 300 ml of adipose tissue (IV administration will be repeated on Day 30).

SVF will be separated from the adipose tissue and cryo-preserved for the placebo group as an option for treatment after the study.
Intervention code [1] 292973 0
Treatment: Other
Comparator / control treatment
Sterile normal saline will be used for the intravenous infusions
Control group
Placebo

Outcomes
Primary outcome [1] 296244 0
Safety will be assessed by monitoring for Adverse Events (including abnormal laboratory test results) over the study interval. Adverse Events will be graded by the Common Terminology Criteria for Adverse Events v 4.0 (CTCAE) and coded according to the Medical Dictionary for Regulatory Activities (MedDRA) terminology

Adverse events monitoring will consist of blood laboratory tests (complete blood count, comprehensive metabolic panel, coagulation and inflammatory), and measurement of vital signs (temperature, heart rate, blood pressure, respiration).
Timepoint [1] 296244 0
Assessed at days 0, 30, 90, 180, 365
Secondary outcome [1] 317957 0
A secondary objective is to measure differences between placebo and SVF based therapies in migraine headache-free days, assessed by headache study diary.
Timepoint [1] 317957 0
At commencement of study and daily with a headache diary until day 365
Secondary outcome [2] 317958 0
Assessment of The Short Form (36) Health Survey a patient-reported survey of patient health and quality life.
Timepoint [2] 317958 0
At commencement of study and days 30, 90, 180 and 365
Secondary outcome [3] 318934 0
A secondary objective is to measure differences between placebo and SVF based therapies in migraine duration, assessed by headache study diary.
Timepoint [3] 318934 0
At commencement of study (90 days prior) and daily with a headache diary until day 365
Secondary outcome [4] 318935 0
A secondary objective is to measure differences between placebo and SVF based therapies in the use of concomitant headache medications, assessed by headache study diary..
Timepoint [4] 318935 0
At commencement of study and daily with a headache diary until day 365
Secondary outcome [5] 318936 0
A secondary objective is to measure differences between placebo and SVF based therapies in migraine headache severity, assessed by visual analogue scale in study diary.
Timepoint [5] 318936 0
At commencement of study and daily with a headache diary until day 365
Secondary outcome [6] 318937 0
A secondary objective is to measure differences between placebo and SVF based therapies in the degree of disability associated symptoms, assessed by headache study diary.
Timepoint [6] 318937 0
At commencement of study and daily with a headache diary until day 365

Eligibility
Key inclusion criteria
Chronic migraine (satisfying the International Classification of Headache Disorders (ICHD-2R) criteria). The ICHD-2R defines chronic migraine as more than fifteen headache days per month over a three month period of which more than eight are migrainous, in the absence of medication over use.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Participants who have received investigational agents within 4 weeks (or 5 half-lives) of treatment.

2. Subjects with significant concurrent or intercurrent illness, psychiatric disorders or alcohol or chemical dependence that would, in the opinion of the Investigator, compromise their safety or compliance or interfere with interpretation of the study.

3. Presence of clinically significant acute or unstable cardiovascular, cerebrovascular (stroke), renal, gastrointestinal, pulmonary, immunological (viral hepatitis, or cirrhosis), endocrine, or central nervous system disorders.

4. Participants who have had active neoplastic disease (cancer) in the previous 3 years.

5. Presence of active infection (except for colds or minor URTI). History of human immunodeficiency virus or acquired immune deficiency syndrome. Significant peripheral vascular disease.

6. Participants who are pregnant or lactating. Female participants who have positive serum beta HCG pregnancy test taken within 7 days before treatment.

7. Fertile participants who are not using effective contraception (e.g., oral contraceptives, intrauterine devices, double barrier methods such as condoms and diaphragms, abstinence or equivalent measures).

8. Previous treatment with SVF.

9. Conditions/therapies/factors which could confound or interfere with the evaluation of pain including but not limited to:
a) Treatments with strong opioid drugs in the previous 60 days for pain
b) Procedures planned during the study period which could interfere with pain assessment (e.g. surgery)
c) Other causes of chronic pain (e.g. neck pain)

10. Use of anticoagulant medication
11. Consistent use of NSAIDs within 48 hours of procedure.
12. Aspirin (except at low dose for cardioprotection), Vitamin E, Fish Oil, krill oil or anti-inflammatories for one week prior
13. Insufficient fat present for liposuction.
14. Inability to understand the study or complete headache diary/ SF-36 questionnaires.
15. Allergic to dimethyl sulfoxide (DMSO)
16. Inability to provide informed consent

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Primarily participants will be recruited from the pool currently existing within the Investigator Practices and by posters in each clinic. Other recruitment for the clinical trial will be via referral from other medical practitioners or limited newspaper/website advertisement in the Sydney and NSW regions.

After direct inquiry from a possible participant or after an initial phone based screen, participants will be invited to attend for a formal assessment to ascertain their suitability for the trial. If suitable they will be invited to enroll in the study and then complete a formal informed consent.

Formally enrolled participants will then be randomly allocated to a study group/arm by the study administrator using a randomisation computer program (www.randomizer.org). Allocation concealment involves contacting the holder of the allocation schedule who is "off-site".
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be allocated a participant number from 1-30 that was randomly generated by (www.randomizer.org)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Those participants allocated to the placebo group will be offered the treatment protocol after completion of study data collection using their cryo-preserved cells. This will be at no charge.
Phase
Phase 2
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
This study is primarily to assess the safety profile of SVF. However, a sample size estimate was undertaken for the secondary exploratory efficacy endpoint that identified a target sample size of 30 patients.

The main efficacy criterion will be an overall mean response of 50% reduction in the headache frequency in the active treatment arm, in comparison to the placebo arm. To allow for attrition and ensure adequate power, a target sample size of at least 30 patients was selected. Loss of diagnostic criteria for migraine headache will be compared between treatment arms using a McNemar’s paired test for categorical data. Headache severity, duration and overall severity scores (severity x duration) will be compared to baseline and summarised using descriptive statistics. VAS scores of perception of headache intensity will be evaluated by the distance along the line (0 to 10), tabulated, and degree of disability analysed using descriptive statistics.

For the sample size estimation, a 30% improvement in the headache diary score from baseline is assumed to be the smallest clinically meaningful change over time. The placebo group is assumed to have a zero improvement over time. The sample sizes have been estimated assuming a power of 80% and an alpha error of 0.05.

The chosen sample size of 30 patients allows for 15 patients per treatment cohort which is sufficient to detect a difference between the placebo group and SVF group in the mean percentage change over time in the headache diary scores of 20% with a standard deviation of 10% or difference of 10% with a much larger standard deviation of 20%.

Recruitment
Recruitment status
Stopped early
Data analysis
No data analysis planned
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
Date of first participant enrolment
Anticipated
30/03/2016
Actual
25/08/2016
Date of last participant enrolment
Anticipated
1/04/2019
Actual
26/09/2017
Date of last data collection
Anticipated
Actual
26/09/2018
Sample size
Target
30
Accrual to date
Final
4
Recruitment in Australia
Recruitment state(s)
QLD,VIC

Funding & Sponsors
Funding source category [1] 292138 0
Charities/Societies/Foundations
Name [1] 292138 0
Migraine Research Foundation
Country [1] 292138 0
United States of America
Funding source category [2] 292139 0
Commercial sector/Industry
Name [2] 292139 0
Cell-Innovations Pty Ltd
Country [2] 292139 0
Australia
Funding source category [3] 292154 0
Commercial sector/Industry
Name [3] 292154 0
Cell-Innovations
Country [3] 292154 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Cell-Innovations
Address
PO Box 7342
WARRINGAH NSW 2100
Country
Australia
Secondary sponsor category [1] 290828 0
None
Name [1] 290828 0
Address [1] 290828 0
Country [1] 290828 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293615 0
Northern Sydney Local Health District
Ethics committee address [1] 293615 0
Ethics committee country [1] 293615 0
Australia
Date submitted for ethics approval [1] 293615 0
30/07/2015
Approval date [1] 293615 0
02/12/2015
Ethics approval number [1] 293615 0
HREC/15/HAWKE/279

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 60694 0
Dr Ralph Bright
Address 60694 0
Macquarie Stem Cells
21b Bathurst St
Liverpool NSw 2170
Country 60694 0
Australia
Phone 60694 0
+61 (2) 9824 3044
Fax 60694 0
Email 60694 0
[email protected]
Contact person for public queries
Name 60695 0
Trial Co-ordinator
Address 60695 0
Cell-Innovations
PO Box 7342
WARRINGAH NSW 2100
Country 60695 0
Australia
Phone 60695 0
+61 1300 738 025
Fax 60695 0
Email 60695 0
[email protected]
Contact person for scientific queries
Name 60696 0
Wayne Thomas
Address 60696 0
Cell-Innovations
PO Box 7342
WARRINGAH NSW 2100
Country 60696 0
Australia
Phone 60696 0
+61 (2) 98242933
Fax 60696 0
Email 60696 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data that underlie the results reported in an article after de identification (text, tables, figures and appendices).
When will data be available (start and end dates)?
Beginning 3 months and ending 36 months following an articles publication
Available to whom?
Investigators whose proposed use of the data has been approved by an independent review committee (learned intermediary) identified for this purpose.
Available for what types of analyses?
For individual participant data meta-analysis
How or where can data be obtained?
Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our data warehouse but without investigator support other than deposited metadata. Information regarding submitting proposals and accessing data may be found at (link to be provided)


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.