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Trial registered on ANZCTR


Registration number
ACTRN12615001339549
Ethics application status
Approved
Date submitted
3/12/2015
Date registered
8/12/2015
Date last updated
11/04/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect on Migraine Frequency of using Combined Anti-oxidant Therapy: N-acetylcysteine, Vitamin E and Vitamin C (NEC): The MIGRANT study.
Scientific title
Effect on Migraine Frequency of using Combined Anti-oxidant Therapy: N-acetylcysteine, Vitamin E and Vitamin C (NEC) in adults with frequent migraine: The MIGRANT study.
Secondary ID [1] 288064 0
NIL
Universal Trial Number (UTN)
U1111-1177-2527
Trial acronym
MIGRANT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Migraine 296933 0
Headaches 296936 0
Condition category
Condition code
Neurological 297178 297178 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
We will study 84 subjects to see if a combination of N-acetylcysteine 600 mg, Vitamin E 250 IU and vitamin C 500 mg (NEC) taken twice daily as oral tablets for 12 weeks, will reduce migraine attacks frequency.

Compliance will be monitored with pill count of returned medication containers and diary filled in by subjects, with 4 weekly investigator compliance interview.
Intervention code [1] 293382 0
Prevention
Intervention code [2] 293383 0
Treatment: Drugs
Comparator / control treatment
Sham-placebo microcellulose tablet administered twice daily for 12 weeks
Control group
Placebo

Outcomes
Primary outcome [1] 296778 0
Difference in mean number of migraine episodes per month between baseline and final four weeks of the study, for both study groups. This will be assessed by a specific questionnaire and data collection sheet for this study, based on data collected from a daily headache diary in compliance with International Headache Society recommendation 2013. Headache Classification Committee of the International Headache Society (IHS).The International Classification of Headache Disorders (3rd Ed) (beta version). Cephalalgia 2013; 33(9): 629–808.
Timepoint [1] 296778 0
4 weeks baseline period for collection of baseline headache data, followed by 12 weeks interventional period; administration of active or placebo drug, as randomised parallel control arm; total of 16 weeks. Outcomes assessed in the final 4 weeks of the 12 week intervention period and compared with outcomes measured in initial 4 week baseline period.
Primary outcome [2] 296779 0
Difference in mean number of migraine days per month between baseline and final four weeks of the study, for both study groups. This will be assessed by a specific questionnaire and data collection sheet for this study, based on data collected from a daily headache diary in compliance with International Headache Society recommendation 2013.
Timepoint [2] 296779 0
4 weeks baseline period for collection of baseline headache data, followed by 12 weeks interventional period; administration of active or placebo drug, as randomised parallel control arm; total of 16 weeks. Outcomes assessed in the final 4 weeks of the 12 week intervention period and compared with outcomes measured in initial 4 week baseline period.
Primary outcome [3] 296780 0
Responder rate: Percentage of subjects reporting at least a 30% reduction in migraine episodes per month between baseline and final four weeks of the study, for both study groups. This will be assessed by a specific questionnaire and data collection sheet for this study, based on data collected from a daily headache diary in compliance with International Headache Society recommendation 2013.
Timepoint [3] 296780 0
4 weeks baseline period for collection of baseline headache data, followed by 12 weeks interventional period; administration of active or placebo drug, as randomised parallel control arm; total of 16 weeks. Outcomes assessed in the final 4 weeks of the 12 week intervention period and compared with outcomes measured in initial 4 week baseline period.
Secondary outcome [1] 319330 0
Difference in mean migraine duration (hours) per month between baseline and final four weeks of the study, for both study groups. This will be assessed by a specific questionnaire and data collection sheet for this study, based on data collected from a daily headache diary in compliance with International Headache Society recommendation 2013.
Timepoint [1] 319330 0
4 weeks baseline period for collection of baseline headache data, followed by 12 weeks interventional period; administration of active or placebo drug, as randomised parallel control arm; total of 16 weeks. Outcomes assessed in the final 4 weeks of the 12 week intervention period and compared with outcomes measured in initial 4 week baseline period.
Secondary outcome [2] 319331 0
Difference in mean migraine severity score per month (categorical scale; 0 = nil, 1 = mild, 2 = moderate, 3 = severe) between baseline and final four weeks of the study, for both study groups. This will be assessed by a specific questionnaire and data collection sheet for this study, based on data collected from a daily headache diary in compliance with International Headache Society recommendation 2013.
Timepoint [2] 319331 0
4 weeks baseline period for collection of baseline headache data, followed by 12 weeks interventional period; administration of active or placebo drug, as randomised parallel control arm; total of 16 weeks. Outcomes assessed in the final 4 weeks of the 12 week intervention period and compared with outcomes measured in initial 4 week baseline period.
Secondary outcome [3] 319332 0
Difference in mean MIDAS per month between baseline and final four weeks of the study, for both study groups. (Migraine Disability Assessment Score). This will be assessed by a specific questionnaire and data collection sheet for this study, based on data collected from a daily headache diary in compliance with International Headache Society recommendation 2013.
Timepoint [3] 319332 0
4 weeks baseline period for collection of baseline headache data, followed by 12 weeks interventional period; administration of active or placebo drug, as randomised parallel control arm; total of 16 weeks. Outcomes assessed in the final 4 weeks of the 12 week intervention period and compared with outcomes measured in initial 4 week baseline period.

Eligibility
Key inclusion criteria
1. Migraine of at least one year’s duration, with onset before 50 years of age.
2. Two-to-eight migraine episodes, and less than six ‘other’ headache types per month, averaged over 12 weeks prior to recruitment.
3. Subjects able to clearly distinguish between migraine and ‘other’ headache types.
4. Cognitive and English language skills allowing completion of headache diaries and self-administration of trial drugs.
Minimum age
18 Years
Maximum age
65 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Participation in a concurrent research trial.
1. Chronic daily headaches, according to IHS 2013..Headache Classification Committee of the International Headache Society (IHS).The International Classification of Headache Disorders (3rd Ed) (beta version). Cephalalgia 2013; 33(9): 629–808.
2. Medication-overuse headache and/or other primary headache disorders, according to IHS 2013 criteria.
3. Change in migraine treatment in the twelve weeks prior to, or during the study.
4. Taking 2 or more migraine prevention drugs, .
5. Failure to respond in 2 or more previous migraine prevention trials.
6. Taking NAc, VitE or VitC supplements in the 12 weeks prior to the study.
7. Pregnancy, or risk of pregnancy during the study; female of reproductive age not taking medically prescribed contraception; breast feeding.
8. Adverse reactions to NAc, VitE or VitC preparations; VitC deficiency.
9. Renal dysfunction (eGFR less than 30 ml/min/1.73m2), liver dysfunction (ALT or AST > 300 IU/L).
10. Clinical risks associated with bleeding, coagulopathy, warfarin therapy.
11. Haemochromatosis, glucose-6-phosphate dehydrogenase deficiency.
12. Daily opioid use in the 12 weeks prior to or during the study.
13. Substance abuse, dependence or addiction during the study.
14. Psychosis, bipolar affective disorder.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
sealed opaque envelopes
numbered containers
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis
Statistical analysis: Analysis by an independent, blinded biostatistician from the UNDA School of Medicine Health Research Institute, Fremantle WA, using SAS 'registered trademark' version 9.2 statistical software (Cary NC, USA) and Excel spreadsheet 2007 'trademark' (Redmond WA, USA) statistical packages. Analysis of outcomes will be performed on the intention-to-treat population. Some post hoc analysis of data may be performed. Significance level: p<0.05; confidence limits of 95%.
Data sets: Demographic, clinical, outcomes data.
Descriptive data: Frequencies, percentages (categorical data); means, standard deviations, confidence intervals (continuous data).
Comparative data analysis: Student’s t test for continuous data; Chi square test for categorical data; confidence intervals; linear or logistic regression
Power calculation
The population for an adequately powered RCT was calculated from data of similar studies in migraine prevention.. It is estimated that 60% of subjects in the active study group and 30% in the placebo-control group will report a ‘positive outcome’ (30% reduction in headache frequency, from baseline). With 80% power and p<0.05, the study population for this RCT is 84 subjects. An interim proof-of-concept (pilot) analysis will be performed when 40 subjects (20 in each group) complete the study, based on guidelines for pilot studies by Lancaster GA, Dodd S, Williamson PR. Design and analysis of pilot studies: recommendations for good practice. Journal of Evaluation in Clinical Practice 2004; 10: 307–312.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
8/04/2016
Actual
Date of last participant enrolment
Anticipated
1/03/2017
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
84
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,WA
Recruitment hospital [1] 4847 0
Joondalup Health Campus - Joondalup
Recruitment hospital [2] 4848 0
St Vincent's Private Hospital (Darlinghurst) - Darlinghurst
Recruitment postcode(s) [1] 12348 0
6027 - Joondalup
Recruitment postcode(s) [2] 12349 0
2010 - Darlinghurst

Funding & Sponsors
Funding source category [1] 292500 0
Charities/Societies/Foundations
Name [1] 292500 0
Fremantle Hospital Medical Research Foundation
Country [1] 292500 0
Australia
Primary sponsor type
University
Name
University of Notre Dame Australia
Address
School on Medicine UNDA, Henry Street, Fremantle WA, PO Box 1225 Fremantle WA 6959
Country
Australia
Secondary sponsor category [1] 291209 0
University
Name [1] 291209 0
Murdoch University
Address [1] 291209 0
School of Psychology, Murdoch University, 90 South Street, Murdoch WA 6150
Country [1] 291209 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293969 0
University of Notre Dame Australia Human Research Ethics Committee
Ethics committee address [1] 293969 0
Ethics committee country [1] 293969 0
Australia
Date submitted for ethics approval [1] 293969 0
10/12/2015
Approval date [1] 293969 0
18/02/2016
Ethics approval number [1] 293969 0
016003F

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 834 834 0 0
/AnzctrAttachments/369726-MIGRANT STUDY Call for Volunteers.pdf

Contacts
Principal investigator
Name 61962 0
Prof Eric John Visser
Address 61962 0
School on Medicine UNDA, Henry Street Fremantle WA, PO Box 1225 Fremantle WA 6959
Country 61962 0
Australia
Phone 61962 0
+618 94009020
Fax 61962 0
Email 61962 0
eric.visser@nd.edu.au
Contact person for public queries
Name 61963 0
Eric John Visser
Address 61963 0
School on Medicine UNDA, Henry Street Fremantle WA, PO Box 1225 Fremantle WA 6959
Country 61963 0
Australia
Phone 61963 0
+618 94009020
Fax 61963 0
Email 61963 0
ndvitmigraine@gmail.com
Contact person for scientific queries
Name 61964 0
Eric John Visser
Address 61964 0
School on Medicine UNDA, Henry Street Fremantle WA, PO Box 1225 Fremantle WA 6959
Country 61964 0
Australia
Phone 61964 0
+618 94009020
Fax 61964 0
Email 61964 0
eric.visser@nd.edu.au

No information has been provided regarding IPD availability


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
SourceTitleYear of PublicationDOI
EmbaseReduction in Migraine and Headache Frequency and Intensity With Combined Antioxidant Prophylaxis (N-acetylcysteine, Vitamin E, and Vitamin C): A Randomized Sham-Controlled Pilot Study.2020https://dx.doi.org/10.1111/papr.12902
N.B. These documents automatically identified may not have been verified by the study sponsor.