Randomised Controlled Trial of Memantine in Fibromyalgia

Fibromyalgia Clinical Trial

Official title:

Efficacy of Memantine in the Treatment of Fibromyalgia: a Double-blind Randomized Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01653457
• Other study ID #: EC11-387
• Status: Not yet recruiting
• Phase: Phase 3
• First received: July 6, 2012
• Last updated: July 30, 2012
• Start date: September 2012
• Est. completion date: May 2013

Study information

• Verified date: July 2012
• Source: Aragon Institute of Health Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: Spain: Spanish Agency of Medicines
• Study type: Interventional

Clinical Trial Summary

Fibromyalgia (FM) is a chronic rheumatic disease of high prevalence and great clinical impact. However, the treatment for FM has limited efficacy, with an effect size of about 0.5. Recent studies have found raised levels of glutamate in the insula, hippocampus and posterior cingulate cortex regions of the brain. This has led a number of authors to suggest the usefulness of glutamate blocking drugs in the treatment of FM.

Aims: To evaluate the efficacy of memantine in the treatment of pain and other symptoms of FM and to assess its efficacy in reducing brain glutamate levels in patients with FM. Material and methods: Randomized controlled trial, of six months duration (including a dose adjustment period of one month). 60 patients with FM will be recruited for inclusion in the study upon fulfillment of selection criteria, and they will be randomized in two groups: A) Treatment group (n=30), will receive 20 mg of memantine o.d ; B) Control group (n=30) will receive placebo. The main objective is to assess the efficacy of memantine in the treatment of pain (pain threshold, pain perception) and other symptoms in fibromyalgia (cognitive state, health status, state of anxiety and depression, quality of life and perceived improvement. Discussion: There is a need for the development of innovative and more effective alternatives for the treatment of FM. This clinical trial will determine whether memantine can be considered as an option in the treatment of FM patients.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: May 2013
• Est. primary completion date: October 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

1. Male or female aged between 18 and 65 years.

2. Ability to understand Spanish.

3. Diagnosis of fibromyalgia carried out by a rheumatologist according to the American College of rheumatology criteria (ACR1990).

4. Ability to read and understand the Patient Information Sheet

5. Signature of Informed Consent Form.

6 .In the case of women of childbearing age, commitment not to become pregnant during the entire duration of the study.

Exclusion Criteria:

1. Undergoing drug treatment for fibromyalgia. Patients undergoing treatment for fibromyalgia will stop treatment and perform a washout period of one week. During that week the patient may take, if necessary, analgesic such as paracetamol, ibuprofen and other NSAIDS to minimize the influence of medication on brain imaging.

2. Currently taking memantine or having taken memantine during the 2 months prior to recruitment.

3. Another Axis I psychiatric disorder using SCID-I that might hinder adherence to the protocol (e.g.: dementia, alcohol and/or substance abuse/dependence, schizophrenia, chronic delirium, acute depression).

4. Pregnancy or breast-feeding.

5. Hypersensitivity to the active ingredient, memantine, or to the excipients.

6. Medical conditions that require special precautions when administering memantine according to the summary of product characteristics:

• Epilepsy.

• Circumstances that may cause high urine pH owing to Proteus urinary infection, renal tubular acidosis or vegetarian diet, recent myocardial infarction, congestive heart disease and uncontrolled arterial hypertension.

7. Clinically significant and active evidence of liver or kidney disease, haematological, respiratory, endocrine or cardiovascular disease or disorders (patients with controlled diabetes and patients with controlled hypertension and complete or incomplete right bundle branch block can be included in the study).

8. Use of prescription drugs that may cause relevant drug interactions with memantine according to the summary of product characteristics: NMDAR antagonists (amantadine, ketamine, dextromethorphan), L-Dopa, dopamine agonists and cholinergic agonists.

9. Use of non-permitted concomitant medication during the week prior to the first evaluation visit or when the patient is expected to require treatment (with at least one of the drugs not permitted during the study): antidepressants (duloxetine, venlafaxine, mirtazapine, bupropion, SSRI, etc.), analgesics (pregabalin, gabapentin, opiates, etc.)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fibromyalgia
• Myofascial Pain Syndromes

Intervention

Drug:
• Memantine
Patients randomised to this arm will receive memantine 20 mg daily. This dose will be reached following this schema: 1st week: 5 mg daily 2nd week: 10 mg daily 3rd week: 15 mg daily From 4th week up to 24th week: 20 mg daily
• Placebo
Patients randomised to this group will receive film-coated placebo tablets (similar to drug tablets.

Locations

Country	Name	City	State
Spain	Mental Health Unit, Primary Care Center "Torrero".	Zaragoza

Sponsors (1)

Lead Sponsor	Collaborator
Aragon Institute of Health Sciences

Country where clinical trial is conducted

Spain, 

References & Publications (31)

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* Note: There are 31 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in pain threshold at month 1	It will be measured by sphygmomanometry, a clinical test widely used and very efficient to identify patients with fibromyalgia.	Month 1	No
Primary	Change from baseline in pain threshold at month 3	It will be measured by sphygmomanometry, a clinical test widely used and very efficient to identify patients with fibromyalgia. Pain perception will be evaluated with the Pain Visual Analogue Scale (VAS pain). It is a horizontal line, 10 cm in length, anchored by word descriptors at each end (no pain and very severe pain)	Month 3	No
Primary	Change from baseline in pain threshold at month 6	It will be measured by sphygmomanometry, a clinical test widely used and very efficient to identify patients with fibromyalgia.	Month 6	No
Primary	Change from baseline in pain perception at month 1	Pain perception will be evaluated with the Pain Visual Analogue Scale (VAS pain). It is a horizontal line, 10 cm in length, anchored by word descriptors at each end (no pain and very severe pain)	Month 1	No
Primary	Change from baseline in pain perception at month 3	Pain perception will be evaluated with the Pain Visual Analogue Scale (VAS pain). It is a horizontal line, 10 cm in length, anchored by word descriptors at each end (no pain and very severe pain)	Month 3	No
Primary	Change from baseline in pain perception at month 6	Pain perception will be evaluated with the Pain Visual Analogue Scale (VAS pain). It is a horizontal line, 10 cm in length, anchored by word descriptors at each end (no pain and very severe pain)	Month 6	No
Secondary	To assess improvement in cognitive state	It will be measured by the Cognition Mini-Exam (MEC).In people under 65 years old, like the population in our study, the threshold that suggests a "probable case" is <27 points. The Spanish version of the questionnaire will be used.; Cognitive state will also be measured by qEEG event-related desynchronization (ERD) at absolute power of upper alpha rhythms in the parieto-occipital region while cognitive tasks are performed.	Baseline, month 1, month 3 and month 6	No
Secondary	To assess improvement in Health Status	It will be evaluated with the Fibromyalgia Impact Questionnaire (FIQ). FIQ is a 10-Item self-questionnaire to measure the Health Status in patients with fibromyalgia. The Spanish version will be used.	Baseline, month 1, month 3 and month 6	No
Secondary	To assess Anxiety and depression levels	This will be evaluated with the Hospital Anxiety Depression Scale (HADS).Spanish version will be used.	Baseline, month 1, month 3 and month 6	No
Secondary	To assess Quality of life	It will be measured by the EuroQol 5D questionnaire. Spanish version will be used.	Baseline, month 1, month 3 and month 6	No
Secondary	To assess Clinical Global Impression	It will be evaluated with the Clinical Global Impression scale.	Baseline, month 1, month 3 and month 6	No
Secondary	Glutamate levels in different brain regions (insula, hippocampus and posterior cingulate cortex).	This will be assessed with magnetic resonance spectroscopy (MRS) and by quantitative encephalography and electroencephalic cordance.	Baseline, month 6	No