Comparison of Therapeutic Effects of Greater Occipital Nerve Block, Topiramate, and Flunarizine on Episodic Migraine

• Sponsor: Ataturk University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03712917
• Collaborator: (none)
• Enrollment: 120
• Location: 1
• Arms: 3
• Actual Duration (Days): 30
• Patients Per Site Per Month: 121.8

Study Details

Study Description

Brief Summary

Background: Preventive drug therapy in migraine aims to reduce the attack frequency, severity and duration of headache. Flunarizine and topiramate are widely used in the prevention of migraine attacks. Greater occipital nerve block (GONB) is an alternative treatment option for the prophylactic treatment of migraine. In this study, investigators compared the effectiveness of GONB, topiramate, and flunarizine in terms of reduction in post-treatment VAS scores and attack frequencies in patients with episodic migraine in a four-week period.

Material and Methods: At least one hundred and twenty migraine patients are aimed to be randomly divided into three treatment groups, namely flunarizine (n=40, estimated), topiramate (n=40, estimated) and GONB (n=40, estimated). The patients will be followed up for four weeks and the attack frequencies and VAS scores will be recorded weekly. At the end of the fourth week, the response rates based on 50% and 75% or more reduction in the VAS scores and attack frequencies will be calculated. Group-wise comparisons will be assessed statistically.

Condition or Disease	Intervention/Treatment	Phase
Migraine	Procedure: Greater Occipital Nerve Block; Drug: Topiramate; Drug: Flunarizine	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 120 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: Comparison of Therapeutic Effects of Greater Occipital Nerve Block, Topiramate, and Flunarizine on Episodic Migraine: A Randomised Parallel Group Study
• Actual Study Start Date: Mar 1, 2019
• Actual Primary Completion Date: Mar 31, 2019
• Actual Study Completion Date: Mar 31, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Greater Occipital Nerve Block The GONB solution is prepared with 1 ml triamcinolone (40mg), 2 ml bupivacaine (10 mg), and 1 ml 0,9% NaCl. The solution is administered using a 22G × 1¼" (0.7 × 40mm) injector with the patient lying prone on the table. Injection is applied to medial of the occipital artery localized at the medial one-third of the superior nuchal line between the occipital tubercle and mastoid process. The scalp is cleaned with iodine before the procedure, and the injections are performed bilaterally at a volume of 2 mL after negative aspiration for blood.	Procedure: Greater Occipital Nerve Block; An enjection to paralyze the occipital nerve.
Active Comparator: Topiramate Topiramate is administered twice a day at a dose of 25 mg/day, which is increased to 100 mg/day in the second week.	Drug: Topiramate; An antiepileptic agent used for migraine prophylaxis.
Active Comparator: Flunarizine Flunarizine is introduced with a single dose of 10 mg/day.	Drug: Flunarizine; A calcium overload blocker agent used for migraine prophylaxis.

Outcome Measures

Primary Outcome Measures

1. Visual Analog Scale [Post treatment 4 weeks]

   Range Pain 0-10, 0: No pain, 10: Worst Pain

2. Attack Frequencies [Post treatment 4 weeks]

   Number of headaches patients suffer in a month.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years to 45 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Migraine diagnosis according to ICHD-2

2. Ages between 15 -45 Volunteering

3. Monthly attack number between 5-14

4. BMI between 18-30

5. w/o history of nephrolithiasis

6. w/o history of DM, peripheral vascular disease

7. w/o history of chronic systemic diseases (lung, heart,liver, kidney)

8. w/o any detected CNS disease (including MS, movement disorders, CVD, primary or secondary tumors)

9. w/o history of acute or chronic psychiatric disease

10. w/o history of antiplatelet and anticoagulant medication

11. w/o any combination of medication overuse headache or other primary headaches

12. w/o previous medication of flunarizine and topiramate

13. w/o previous application of GONB

Exclusion Criteria:

1. Pregnancy

2. Lost to follow up

• exited with his/her own will

• detected primary headache during follow up

• cessation due to adverse effects of topiramate

• cessation due to adverse effects of flunarizine

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ataturk University Resarch Hospital	Erzurum		Turkey	25000

Sponsors and Collaborators

• Ataturk University

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 7, 2019

More Information

Publications

• Baker C. Double-blind evaluation of flunarizine and placebo in the prophylactic treatment of migraine. Headache 1987; 27:288.
• Bovim G, Sand T. Cervicogenic headache, migraine without aura and tension-type headache. Diagnostic blockade of greater occipital and supra-orbital nerves. Pain. 1992 Oct;51(1):43-48. doi: 10.1016/0304-3959(92)90007-X.
• Diener H-C, Goadsby PJ. Migraine In: Brandt T, Caplan L, Dichgans J, Diener H-C, Kennard C (eds) Course and treatment of neurological disorders. 2nd edition. Academic Press, San Diego, (2003). pp 1-16.
• Silberstein SD, Neto W, Schmitt J, Jacobs D; MIGR-001 Study Group. Topiramate in migraine prevention: results of a large controlled trial. Arch Neurol. 2004 Apr;61(4):490-5.

• Responsible Party: Mustafa Ceylan, Principal İnvastigator, Ataturk University
• ClinicalTrials.gov Identifier: NCT03712917
• Other Study ID Numbers: 2019/22-3
• First Posted: Oct 19, 2018
• Last Update Posted: Jan 21, 2020
• Last Verified: Jan 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Mustafa Ceylan, Principal İnvastigator, Ataturk University: Migraine; Greater Occipital Nerve Block; Topiramate; Flunarizine
• Additional relevant MeSH terms: Migraine Disorders; Topiramate; Flunarizine

Study Results

Participant Flow

Arm/Group Title	Greater Occipital Nerve Block	Topiramate	Flunarizine
Arm/Group Description	The GONB solution is prepared with 1 ml triamcinolone (40mg), 2 ml bupivacaine (10 mg), and 1 ml 0,9% NaCl. The solution is administered using a 22G × 1¼" (0.7 × 40mm) injector with the patient lying prone on the table. Injection is applied to medial of the occipital artery localized at the medial one-third of the superior nuchal line between the occipital tubercle and mastoid process. The scalp is cleaned with iodine before the procedure, and the injections are performed bilaterally at a volume of 2 mL after negative aspiration for blood. Greater Occipital Nerve Block: An enjection to paralyze the occipital nerve.	Topiramate is administered twice a day at a dose of 25 mg/day, which is increased to 100 mg/day in the second week. Topiramate: An antiepileptic agent used for migraine prophylaxis.	Flunarizine is introduced with a single dose of 10 mg/day. Flunarizine: A calcium overload blocker agent used for migraine prophylaxis.
Period Title: Overall Study
STARTED	40	40	40
COMPLETED	31	32	31
NOT COMPLETED	9	8	9

Baseline Characteristics

Arm/Group Title	Greater Occipital Nerve Block	Topiramate	Flunarizine	Total
Arm/Group Description	The GONB solution is prepared with 1 ml triamcinolone (40mg), 2 ml bupivacaine (10 mg), and 1 ml 0,9% NaCl. The solution is administered using a 22G × 1¼" (0.7 × 40mm) injector with the patient lying prone on the table. Injection is applied to medial of the occipital artery localized at the medial one-third of the superior nuchal line between the occipital tubercle and mastoid process. The scalp is cleaned with iodine before the procedure, and the injections are performed bilaterally at a volume of 2 mL after negative aspiration for blood. Greater Occipital Nerve Block: An enjection to paralyze the occipital nerve.	Topiramate is administered twice a day at a dose of 25 mg/day, which is increased to 100 mg/day in the second week. Topiramate: An antiepileptic agent used for migraine prophylaxis.	Flunarizine is introduced with a single dose of 10 mg/day. Flunarizine: A calcium overload blocker agent used for migraine prophylaxis.	Total of all reporting groups
Overall Participants	40	40	40	120
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30.2 (8.9)	31.5 (8.2)	30.9 (9.0)	30.9 (8.6)
Sex: Female, Male (Count of Participants)
Female	22 55%	26 65%	24 60%	72 60%
Male	9 22.5%	6 15%	7 17.5%	22 18.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%	0 0%
White	40 100%	40 100%	40 100%	120 100%
More than one race	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Visual Analog Scale
Description	Range Pain 0-10, 0: No pain, 10: Worst Pain
Time Frame	Post treatment 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Greater Occipital Nerve Block	Topiramate	Flunarizine
Arm/Group Description	The GONB solution is prepared with 1 ml triamcinolone (40mg), 2 ml bupivacaine (10 mg), and 1 ml 0,9% NaCl. The solution is administered using a 22G × 1¼" (0.7 × 40mm) injector with the patient lying prone on the table. Injection is applied to medial of the occipital artery localized at the medial one-third of the superior nuchal line between the occipital tubercle and mastoid process. The scalp is cleaned with iodine before the procedure, and the injections are performed bilaterally at a volume of 2 mL after negative aspiration for blood. Greater Occipital Nerve Block: An enjection to paralyze the occipital nerve.	Topiramate is administered twice a day at a dose of 25 mg/day, which is increased to 100 mg/day in the second week. Topiramate: An antiepileptic agent used for migraine prophylaxis.	Flunarizine is introduced with a single dose of 10 mg/day. Flunarizine: A calcium overload blocker agent used for migraine prophylaxis.
Measure Participants	31	32	31
Pretreatment	8.1 (1.0)	7.9 (0.9)	7.9 (0.9)
Posttreatment	5.9 (1.6)	5.5 (2.1)	5.3 (1.7)

2. Primary Outcome

Title	Attack Frequencies
Description	Number of headaches patients suffer in a month.
Time Frame	Post treatment 4 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Greater Occipital Nerve Block	Topiramate	Flunarizine
Arm/Group Description	The GONB solution is prepared with 1 ml triamcinolone (40mg), 2 ml bupivacaine (10 mg), and 1 ml 0,9% NaCl. The solution is administered using a 22G × 1¼" (0.7 × 40mm) injector with the patient lying prone on the table. Injection is applied to medial of the occipital artery localized at the medial one-third of the superior nuchal line between the occipital tubercle and mastoid process. The scalp is cleaned with iodine before the procedure, and the injections are performed bilaterally at a volume of 2 mL after negative aspiration for blood. Greater Occipital Nerve Block: An enjection to paralyze the occipital nerve.	Topiramate is administered twice a day at a dose of 25 mg/day, which is increased to 100 mg/day in the second week. Topiramate: An antiepileptic agent used for migraine prophylaxis.	Flunarizine is introduced with a single dose of 10 mg/day. Flunarizine: A calcium overload blocker agent used for migraine prophylaxis.
Measure Participants	31	32	31
Pretreatment	8.6 (2.6)	8.0 (2.7)	8.0 (2.4)
Posttreatment	3.3 (1.0)	2.7 (2.3)	2.8 (1.4)

Adverse Events

Time Frame	From the start of the study till the end (one month)
Arm/Group Title	Greater Occipital Nerve Block		Topiramate		Flunarizine
Arm/Group Description	The GONB solution is prepared with 1 ml triamcinolone (40mg), 2 ml bupivacaine (10 mg), and 1 ml 0,9% NaCl. The solution is administered using a 22G × 1¼" (0.7 × 40mm) injector with the patient lying prone on the table. Injection is applied to medial of the occipital artery localized at the medial one-third of the superior nuchal line between the occipital tubercle and mastoid process. The scalp is cleaned with iodine before the procedure, and the injections are performed bilaterally at a volume of 2 mL after negative aspiration for blood. Greater Occipital Nerve Block: An enjection to paralyze the occipital nerve.		Topiramate is administered twice a day at a dose of 25 mg/day, which is increased to 100 mg/day in the second week. Topiramate: An antiepileptic agent used for migraine prophylaxis.		Flunarizine is introduced with a single dose of 10 mg/day. Flunarizine: A calcium overload blocker agent used for migraine prophylaxis.
All Cause Mortality
	Greater Occipital Nerve Block		Topiramate		Flunarizine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/40 (0%)		0/40 (0%)
Serious Adverse Events
	Greater Occipital Nerve Block		Topiramate		Flunarizine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		0/40 (0%)		0/40 (0%)
Other (Not Including Serious) Adverse Events
	Greater Occipital Nerve Block		Topiramate		Flunarizine
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/40 (0%)		4/40 (10%)		3/40 (7.5%)
Nervous system disorders
Sedation	0/40 (0%)	0	0/40 (0%)	0	3/40 (7.5%)	3
Fatique	0/40 (0%)	0	1/40 (2.5%)	1	0/40 (0%)	0
paresthesia	0/40 (0%)	0	1/40 (2.5%)	1	0/40 (0%)	0
memory difficulties	0/40 (0%)	0	2/40 (5%)	2	0/40 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.