ANZCTR - Registration

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]

NIL

Universal Trial Number (UTN)

U1111-1177-2527

Trial acronym

MIGRANT

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Migraine

Headaches

Condition category

Condition code

Neurological

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]

Prevention

Intervention code [2]

Treatment: Drugs

Comparator / control treatment

Sham-placebo microcellulose tablet administered twice daily for 12 weeks

Control group

Placebo

Outcomes

Primary outcome [1]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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]

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

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]

Joondalup Health Campus - Joondalup

Recruitment hospital [2]

St Vincent's Private Hospital (Darlinghurst) - Darlinghurst

Recruitment postcode(s) [1]

6027 - Joondalup

Recruitment postcode(s) [2]

2010 - Darlinghurst

Funding & Sponsors

Funding source category [1]

Charities/Societies/Foundations

Name [1]

Fremantle Hospital Medical Research Foundation

Country [1]

Australia

Primary sponsor type

University

Name

University of Notre Dame Australia

Country

Australia

Secondary sponsor category [1]

University

Name [1]

Murdoch University

Country [1]

Australia

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

University of Notre Dame Australia Human Research Ethics Committee

Ethics committee address [1]

School on Medicine UNDA, Henry Street, Fremantle WA, PO Box 1225 Fremantle WA 6959

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

10/12/2015

Approval date [1]

18/02/2016

Ethics approval number [1]

016003F

Summary

Brief summary

Effects on Migraine Frequency using Combined Anti-oxidant Therapy: N-acetylcysteine, Vitamin E and Vitamin C (NEC): The MIGRANT study.

Lay title: Using a combination of anti-oxidant supplements N-acetylcysteine, Vitamin E and Vitamin C to reduce the frequency of migraines.

Summary:
Migraine affects 15% of Western Australians and is a leading cause of suffering and disability in our community. Research suggests that inflammation of the brain’s coverings (meninges) by nerve cell inflammation and the release of ‘free radicals’, is a cause of migraine. N-acetylcysteine, Vitamin E and Vitamin C are powerful anti-oxidants (free-radical scavengers) that reduce brain inflammation and nerve activity. It is therefore possible these anti-oxidants could reduce the number and severity of migraines. We will study 90 subjects to see if a combination of N-acetylcysteine 600 mg, Vitamin E 250 IU and vitamin C 500 mg (NEC) taken twice daily for 12 weeks, will reduce migraine attacks. This safe vitamin-based therapy has never been studied and if effective, will play an important role in migraine prevention.

Trial website

http://www.nd.edu.au/fremantle/schools/medicine/churack-chair

Public notes

We are now recruiting for this trial
 if you are interested please email
ndvitmigraine@gmail.com

Attachments [1]

/AnzctrAttachments/369726-MIGRANT STUDY Call for Volunteers.pdf

Contacts

Principal investigator

Name

Prof Eric John Visser

Address

School on Medicine UNDA, Henry Street Fremantle WA, PO Box 1225 Fremantle WA 6959

Country

Australia

Phone

+618 94009020

Email

[email protected]

Contact person for public queries

Name

Eric John Visser

Address

School on Medicine UNDA, Henry Street Fremantle WA, PO Box 1225 Fremantle WA 6959

Country

Australia

Phone

+618 94009020

Email

[email protected]

Contact person for scientific queries

Name

Eric John Visser

Address

School on Medicine UNDA, Henry Street Fremantle WA, PO Box 1225 Fremantle WA 6959

Country

Australia

Phone

+618 94009020

Email

[email protected]

Trial Review

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