Saline Injections for Prophylactic Treatment of Chronic Migraine

Saline Injections for Prophylactic Treatment of Chronic Migraine - a Randomized Controlled Study

In this study, the investigators want to investigate whether saline injections in the neck and head muscles can reduce symptoms of chronic migraine. In existing studies, saline injections (used as placebo treatment) have given patients with chronic migraine an average of 7 headache-free days per month.

Study Overview

• Status: Terminated
• Conditions: Chronic Migraine
• Intervention / Treatment: Drug: Saline injection; Procedure: Placebo

Detailed Description

Patients who meet the diagnostic criteria for chronic migraine will be invited to participate in the study. All participants will undergo a medical examination. The participants will fill out an electronic headache diary for one month. This will give a picture of the current headache pattern and establish a baseline. The participants will then be randomized into two groups: saline injections or needle sticks without injection. They will not be aware of which group they belong to. The treatment will be repeated on two occasions three months apart. The headache diary will continue during the treatment period and up to three months after the second treatment. The effect will be analyzed by comparing baseline data from the headache diary to data after treatment. The primary outcome of the study is the number of days with headache, during a 28-day period.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 4

Contacts and Locations

Study Locations

• Sweden
  • Borås, Sweden
    • Rehabilitation clinic, Southern Älvsborg Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Participants must meet the diagnostic criteria for chronic migraine (headache that have occurred on at least 15 days per month, for at least three months. At least eight of the headache episodes must be typical for migraine).
• Participants must be able to understand and give informed consent to participate in the study.
• Participants must be aged 18-65 years.

Exclusion Criteria:

• Participants must not suffer from other medical conditions that may affect the outcome of the study, including Horton's headache, temporal arteritis, trigeminal neuralgia, chronic paroxysmal hemi-crania, atypical facial pain and headache of unknown cause.
• Participants must not have medical conditions that require use of drugs that can affect the headache pattern (for example rheumatic disorders).
• Participants must not suffer from malignant diseases.
• Participants must not plan to make changes to existing prophylactic headache medication during the study. Patients may, if already on treatment, choose to continue this throughout the course of the study, or choose to stop the prophylactic treatment at least one week before the start of the baseline period.
• Participants must not have an ongoing patient-doctor contact with the physician giving the injections.
• Participants must not have an ongoing patient-doctor contact with the monitor of the study.
• Participants must not have received injection therapy in the face, head or neck muscles (medical or cosmetic) less than three months before the start of the study, nor should they plan such treatment during the course of the study.
• Participants must not be pregnant or plan pregnancy during the course of the study.
• Participants must not breastfeed or plan to do so during the study.
• Participants must not have any contraindications to injection therapy (such as disease with increased bleeding tendency or treatment with certain types of blood thinners).
• Participants must have no difficulty understanding or making themselves understood in Swedish.
• Participants must be able to fill out the headache diary and questionnaires.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sodium chloride injection; Sodium chloride 9mg/ml by injection	Drug: Saline injection; Half of the patients will be randomized to saline injections into the neck and head muscles; Other Names: Sodium chloride Braun; Sodium chloride Fresenius Krabi
Placebo Comparator: Needle sting; Brief needle stings without injection	Procedure: Placebo; Half of the group will be treated with needle stings without injections

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in number of Days with headache	A headache day is defined as: 1) a day with headache ≥ 4 hours or 2) a day with headache of any duration, where the headache is relieved with acute headache medication (AHM) By AHM is meant a drug that is taken when needed for the purpose of relieving headaches, including any of the following: Paracetamol; Aspirin; NSAID; Triptan; Opioid; Ergotamine; Dihydroergotamine The primary efficacy measure is the change between the baseline 28-day period (4 weeks prior injection 1) and the corresponding period during follow-up, i.e. the 28-day period ending the study. a secondary efficacy measure is the change between the baseline and the 28-day period preceding the second injection.	change between baseline 28 day period prior injection1 and 28 day period ending study
Change in number of Days with headache	A headache day is defined as: 1) a day with headache ≥ 4 hours or 2) a day with headache of any duration, where the headache is relieved with acute headache medication. By AHM is meant a drug that is taken when needed for the purpose of relieving headaches, including any of the following: Paracetamol; Aspirin; NSAID; Triptan; Opioid; Ergotamine; Dihydroergotamine The primary efficacy measure is the change between the baseline 28-day period (4 weeks prior injection 1) and the corresponding period during follow-up, i.e. the 28-day period ending the study. a secondary efficacy measure is the change between the baseline and the 28-day period preceding the second injection.	change between baseline and the 28-day period preceding the second injection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Days with moderate or severe headache	A headache day with moderate or severe intensity is defined as: 1) a day with headache ≥ 4 hours and with a peak of moderate or severe intensity or 2) a day with headache of any duration or intensity, where the headache is relieved with AHM. The primary efficacy measure is the change between the baseline 28-day period (4 weeks prior injection 1) and the corresponding period during follow-up, i.e. the 28-day period ending the study. a secondary efficacy measure is the change between the baseline and the 28-day period preceding the second injection.	change between baseline 28 day period prior injection1 and 28 day period ending study
Number of Days with moderate or severe headache	A headache day with moderate or severe intensity is defined as: 1) a day with headache ≥ 4 hours and with a peak of moderate or severe intensity or 2) a day with headache of any duration or intensity, where the headache is relieved with AHM. The primary efficacy measure is the change between the baseline 28-day period (4 weeks prior injection 1) and the corresponding period during follow-up, i.e. the 28-day period ending the study. a secondary efficacy measure is the change between the baseline and the 28-day period preceding the second injection.	change between baseline and the 28-day period preceding the second injection
Number of days with acute headache medication	Number of days the respondent stated that AHM has been taken.The primary efficacy measure is the change between the baseline 28-day period (4 weeks prior injection 1) and the corresponding period during follow-up, i.e. the 28-day period ending the study. a secondary efficacy measure is the change between the baseline and the 28-day period preceding the second injection.	change between baseline 28 day period prior injection1 and 28 day period ending study
Number of days with acute headache medication	Number of days the respondent stated that AHM has been taken.The primary efficacy measure is the change between the baseline 28-day period (4 weeks prior injection 1) and the corresponding period during follow-up, i.e. the 28-day period ending the study. a secondary efficacy measure is the change between the baseline and the 28-day period preceding the second injection.	change between baseline and the 28-day period preceding the second injection
Number of days with acute headache medication that requires prescription	Number of days the respondent stated that he or she has taken acute headache medication that require prescription, ie all drugs in the list in primary outcome above that require prescription by a doctor.The primary efficacy measure is the change between the baseline 28-day period (4 weeks prior injection 1) and the corresponding period during follow-up, i.e. the 28-day period ending the study. a secondary efficacy measure is the change between the baseline and the 28-day period preceding the second injection.	change between baseline 28 day period prior injection1 and 28 day period ending study
Number of days with acute headache medication that requires prescription	Number of days the respondent stated that he or she has taken acute headache medication that require prescription, ie all drugs in the list in primary outcome above that require prescription by a doctor.The primary efficacy measure is the change between the baseline 28-day period (4 weeks prior injection 1) and the corresponding period during follow-up, i.e. the 28-day period ending the study. a secondary efficacy measure is the change between the baseline and the 28-day period preceding the second injection.	change between baseline and the 28-day period preceding the second injection
Change in outcome of disease-specific quality of Life: Migraine-specific Quality of Life Questionnaire (MSQ v2.1)	Change in Migraine-specific Quality of Life Questionnaire (MSQ v2.1)	Change between baseline and 12 weeks after second injection
Change in outcome of disease-specific implications: Headache Impact Test (HIT-6)	Change in Headache Impact Test (HIT-6)	Change between baseline and 12 weeks after second injection

Collaborators and Investigators

• Sponsor: Göteborg University
• Investigators: Principal Investigator: Malin Kim, MD, Rehabilitation clinic, Southern Älvsborg Hospital

Publications and helpful links

General Publications

• Dodick DW, Turkel CC, DeGryse RE, Aurora SK, Silberstein SD, Lipton RB, Diener HC, Brin MF; PREEMPT Chronic Migraine Study Group. OnabotulinumtoxinA for treatment of chronic migraine: pooled results from the double-blind, randomized, placebo-controlled phases of the PREEMPT clinical program. Headache. 2010 Jun;50(6):921-36. doi: 10.1111/j.1526-4610.2010.01678.x. Epub 2010 May 7.
• Cole JC, Lin P, Rupnow MF. Validation of the Migraine-Specific Quality of Life Questionnaire version 2.1 (MSQ v. 2.1) for patients undergoing prophylactic migraine treatment. Qual Life Res. 2007 Sep;16(7):1231-7. doi: 10.1007/s11136-007-9217-1. Epub 2007 Apr 28.
• Freitag FG, Diamond S, Diamond M, Urban G. Botulinum Toxin Type A in the treatment of chronic migraine without medication overuse. Headache. 2008 Feb;48(2):201-9. doi: 10.1111/j.1526-4610.2007.00963.x. Epub 2007 Nov 28.
• Gandek B, Alacoque J, Uzun V, Andrew-Hobbs M, Davis K. Translating the Short-Form Headache Impact Test (HIT-6) in 27 countries: methodological and conceptual issues. Qual Life Res. 2003 Dec;12(8):975-9. doi: 10.1023/a:1026171315263.
• Smelt AF, Assendelft WJ, Terwee CB, Ferrari MD, Blom JW. What is a clinically relevant change on the HIT-6 questionnaire? An estimation in a primary-care population of migraine patients. Cephalalgia. 2014 Jan;34(1):29-36. doi: 10.1177/0333102413497599. Epub 2013 Jul 10.
• Goadsby PJ. Migraine pathophysiology. Headache. 2005 Apr;45 Suppl 1:S14-24. doi: 10.1111/j.1526-4610.2005.4501003.x.
• Kim M, Danielsson A, Ekelund A-C, Kemppainen E, Sjögren P, Svanberg T, Szalo G,Samuelsson O. Title:Botulinum toxin type A for Prophylactic Treatment of Chronic Migraine [Botulinum toxin typ Asom profylaktisk behandling av kronisk migrän]. Göteborg: Västra Götalandsregionen, SahlgrenskaUniversitetssjukhuset, HTA-centrum; 2014. Regional activity-based HTA 2014:70

Study record dates

Study Major Dates

• Study Start (Actual): June 17, 2019
• Primary Completion (Actual): May 21, 2021
• Study Completion (Actual): May 21, 2021

Study Registration Dates

• First Submitted: April 8, 2019
• First Submitted That Met QC Criteria: April 16, 2019
• First Posted (Actual): April 18, 2019

Study Record Updates

• Last Update Posted (Actual): March 31, 2022
• Last Update Submitted That Met QC Criteria: March 17, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Chronic migraine; Saline injection
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Headache Disorders, Primary; Headache Disorders; Migraine Disorders
• Other Study ID Numbers: Migraine1; 2018-003868-32 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No