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Randomised Controlled Trial of Memantine in Fibromyalgia

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified July 2012 by Aragon Institute of Health Sciences.
Recruitment status was:  Not yet recruiting
Sponsor:
ClinicalTrials.gov Identifier:
NCT01653457
First Posted: July 31, 2012
Last Update Posted: July 31, 2012
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
Aragon Institute of Health Sciences
  Purpose

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.


Condition Intervention Phase
Fibromyalgia Drug: Memantine Drug: Placebo Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Efficacy of Memantine in the Treatment of Fibromyalgia: a Double-blind Randomized Trial

Resource links provided by NLM:


Further study details as provided by Aragon Institute of Health Sciences:

Primary Outcome Measures:
  • Change from baseline in pain threshold at month 1 [ Time Frame: Month 1 ]
    It will be measured by sphygmomanometry, a clinical test widely used and very efficient to identify patients with fibromyalgia.

  • Change from baseline in pain threshold at month 3 [ Time Frame: 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)

  • Change from baseline in pain threshold at month 6 [ Time Frame: Month 6 ]
    It will be measured by sphygmomanometry, a clinical test widely used and very efficient to identify patients with fibromyalgia.

  • Change from baseline in pain perception at month 1 [ Time Frame: 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)

  • Change from baseline in pain perception at month 3 [ Time Frame: 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)

  • Change from baseline in pain perception at month 6 [ Time Frame: 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)


Secondary Outcome Measures:
  • To assess improvement in cognitive state [ Time Frame: Baseline, month 1, month 3 and month 6 ]

    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.


  • To assess improvement in Health Status [ Time Frame: Baseline, month 1, month 3 and month 6 ]
    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.

  • To assess Anxiety and depression levels [ Time Frame: Baseline, month 1, month 3 and month 6 ]
    This will be evaluated with the Hospital Anxiety Depression Scale (HADS).Spanish version will be used.

  • To assess Quality of life [ Time Frame: Baseline, month 1, month 3 and month 6 ]
    It will be measured by the EuroQol 5D questionnaire. Spanish version will be used.

  • To assess Clinical Global Impression [ Time Frame: Baseline, month 1, month 3 and month 6 ]
    It will be evaluated with the Clinical Global Impression scale.

  • Glutamate levels in different brain regions (insula, hippocampus and posterior cingulate cortex). [ Time Frame: Baseline, month 6 ]
    This will be assessed with magnetic resonance spectroscopy (MRS) and by quantitative encephalography and electroencephalic cordance.


Estimated Enrollment: 60
Study Start Date: September 2012
Estimated Study Completion Date: May 2013
Estimated Primary Completion Date: October 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo Drug: Placebo
Patients randomised to this group will receive film-coated placebo tablets (similar to drug tablets.
Active Comparator: Memantine 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
Other Name: Ebixa

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01653457


Locations
Spain
Mental Health Unit, Primary Care Center "Torrero". Not yet recruiting
Zaragoza, Spain, 50007
Principal Investigator: José Javier García Campayo, PhD         
Sponsors and Collaborators
Aragon Institute of Health Sciences
Investigators
Principal Investigator: José Javier García Campayo, PhD Miguel Servet University Hospital
  More Information

Publications:
Staud R, Vierck CJ, Robinson ME, Price DD. Effects of the N-methyl-D-aspartate receptor antagonist dextromethorphan on temporal summation of pain are similar in fibromyalgia patients and normal control subjects. J Pain. 2005 May;6(5):323-32.
Graven-Nielsen T, Aspegren Kendall S, Henriksson KG, Bengtsson M, Sörensen J, Johnson A, Gerdle B, Arendt-Nielsen L. Ketamine reduces muscle pain, temporal summation, and referred pain in fibromyalgia patients. Pain. 2000 Apr;85(3):483-91.
Chen HS, Lipton SA. The chemical biology of clinically tolerated NMDA receptor antagonists. J Neurochem. 2006 Jun;97(6):1611-26. Review.
Tariot PN, Farlow MR, Grossberg GT, Graham SM, McDonald S, Gergel I; Memantine Study Group. Memantine treatment in patients with moderate to severe Alzheimer disease already receiving donepezil: a randomized controlled trial. JAMA. 2004 Jan 21;291(3):317-24.
Reisberg B, Doody R, Stöffler A, Schmitt F, Ferris S, Möbius HJ. A 24-week open-label extension study of memantine in moderate to severe Alzheimer disease. Arch Neurol. 2006 Jan;63(1):49-54.
Nikolajsen L, Gottrup H, Kristensen AG, Jensen TS. Memantine (a N-methyl-D-aspartate receptor antagonist) in the treatment of neuropathic pain after amputation or surgery: a randomized, double-blinded, cross-over study. Anesth Analg. 2000 Oct;91(4):960-6.
Weinbroum AA, Rudick V, Paret G, Ben-Abraham R. The role of dextromethorphan in pain control. Can J Anaesth. 2000 Jun;47(6):585-96. Review.
Sinis N, Birbaumer N, Gustin S, Schwarz A, Bredanger S, Becker ST, Unertl K, Schaller HE, Haerle M. Memantine treatment of complex regional pain syndrome: a preliminary report of six cases. Clin J Pain. 2007 Mar-Apr;23(3):237-43.
Hackworth RJ, Tokarz KA, Fowler IM, Wallace SC, Stedje-Larsen ET. Profound pain reduction after induction of memantine treatment in two patients with severe phantom limb pain. Anesth Analg. 2008 Oct;107(4):1377-9. doi: 10.1213/ane.0b013e31817f90f1.
Wolfe F, Smythe HA, Yunus MB, Bennett RM, Bombardier C, Goldenberg DL, Tugwell P, Campbell SM, Abeles M, Clark P, et al. The American College of Rheumatology 1990 Criteria for the Classification of Fibromyalgia. Report of the Multicenter Criteria Committee. Arthritis Rheum. 1990 Feb;33(2):160-72.
Gamero Ruiz F, Gabriel Sánchez R, Carbonell Abello J, Tornero Molina J, Sánchez-Magro I. [Pain in Spanish rheumatology outpatient offices: EPIDOR epidemiological study]. Rev Clin Esp. 2005 Apr;205(4):157-63. Spanish. Erratum in: Rev Clin Esp. 2005 Dec;205(12):600.
Briley M. Drugs to treat fibromyalgia - the transatlantic difference. Curr Opin Investig Drugs. 2010 Jan;11(1):16-8.
Garcia-Campayo J, Magdalena J, Magallón R, Fernández-García E, Salas M, Andrés E. A meta-analysis of the efficacy of fibromyalgia treatment according to level of care. Arthritis Res Ther. 2008;10(4):R81. doi: 10.1186/ar2455. Epub 2008 Jul 15. Review.
Mountz JM, Bradley LA, Modell JG, Alexander RW, Triana-Alexander M, Aaron LA, Stewart KE, Alarcón GS, Mountz JD. Fibromyalgia in women. Abnormalities of regional cerebral blood flow in the thalamus and the caudate nucleus are associated with low pain threshold levels. Arthritis Rheum. 1995 Jul;38(7):926-38.
Kwiatek R, Barnden L, Tedman R, Jarrett R, Chew J, Rowe C, Pile K. Regional cerebral blood flow in fibromyalgia: single-photon-emission computed tomography evidence of reduction in the pontine tegmentum and thalami. Arthritis Rheum. 2000 Dec;43(12):2823-33.
Garcia-Campayo J, Sanz-Carrillo C, Baringo T, Ceballos C. SPECT scan in somatization disorder patients: an exploratory study of eleven cases. Aust N Z J Psychiatry. 2001 Jun;35(3):359-63.
Harris RE, Sundgren PC, Craig AD, Kirshenbaum E, Sen A, Napadow V, Clauw DJ. Elevated insular glutamate in fibromyalgia is associated with experimental pain. Arthritis Rheum. 2009 Oct;60(10):3146-52. doi: 10.1002/art.24849.
Choi DW, Koh JY, Peters S. Pharmacology of glutamate neurotoxicity in cortical cell culture: attenuation by NMDA antagonists. J Neurosci. 1988 Jan;8(1):185-96.
Leuchter AF, Cook IA, Lufkin RB, Dunkin J, Newton TF, Cummings JL, Mackey JK, Walter DO. Cordance: a new method for assessment of cerebral perfusion and metabolism using quantitative electroencephalography. Neuroimage. 1994 Jun;1(3):208-19.
Leuchter AF, Uijtdehaage SH, Cook IA, O'Hara R, Mandelkern M. Relationship between brain electrical activity and cortical perfusion in normal subjects. Psychiatry Res. 1999 Apr 26;90(2):125-40.
Cook IA, Leuchter AF, Morgan ML, Stubbeman W, Siegman B, Abrams M. Changes in prefrontal activity characterize clinical response in SSRI nonresponders: a pilot study. J Psychiatr Res. 2005 Sep;39(5):461-6.
Venneman S, Leuchter A, Bartzokis G, Beckson M, Simon SL, Schaefer M, Rawson R, Newton T, Cook IA, Uijtdehaage S, Ling W. Variation in neurophysiological function and evidence of quantitative electroencephalogram discordance: predicting cocaine-dependent treatment attrition. J Neuropsychiatry Clin Neurosci. 2006 Spring;18(2):208-16.
Hunter AM, Leuchter AF, Morgan ML, Cook IA. Changes in brain function (quantitative EEG cordance) during placebo lead-in and treatment outcomes in clinical trials for major depression. Am J Psychiatry. 2006 Aug;163(8):1426-32.
Evans KC, Dougherty DD, Pollack MH, Rauch SL. Using neuroimaging to predict treatment response in mood and anxiety disorders. Ann Clin Psychiatry. 2006 Jan-Mar;18(1):33-42. Review.
Bares M, Brunovsky M, Kopecek M, Stopkova P, Novak T, Kozeny J, Höschl C. Changes in QEEG prefrontal cordance as a predictor of response to antidepressants in patients with treatment resistant depressive disorder: a pilot study. J Psychiatr Res. 2007 Apr-Jun;41(3-4):319-25. Epub 2006 Aug 4.
Bares M, Brunovsky M, Kopecek M, Novak T, Stopkova P, Kozeny J, Sos P, Krajca V, Höschl C. Early reduction in prefrontal theta QEEG cordance value predicts response to venlafaxine treatment in patients with resistant depressive disorder. Eur Psychiatry. 2008 Aug;23(5):350-5. doi: 10.1016/j.eurpsy.2008.03.001. Epub 2008 May 2.
Vargas A, Vargas A, Hernández-Paz R, Sánchez-Huerta JM, Romero-Ramírez R, Amezcua-Guerra L, Kooh M, Nava A, Pineda C, Rodríguez-Leal G, Martínez-Lavín M. Sphygmomanometry-evoked allodynia--a simple bedside test indicative of fibromyalgia: a multicenter developmental study. J Clin Rheumatol. 2006 Dec;12(6):272-4.
Sriwatanakul K, Kelvie W, Lasagna L, Calimlim JF, Weis OF, Mehta G. Studies with different types of visual analog scales for measurement of pain. Clin Pharmacol Ther. 1983 Aug;34(2):234-9.
Lobo A, Saz P, Marcos G, Día JL, de la Cámara C, Ventura T, Morales Asín F, Fernando Pascual L, Montañés JA, Aznar S. [Revalidation and standardization of the cognition mini-exam (first Spanish version of the Mini-Mental Status Examination) in the general geriatric population]. Med Clin (Barc). 1999 Jun 5;112(20):767-74. Spanish. Erratum in: Med Clin (Barc) 1999 Jul 10;113(5):197.
Klimesch W, Doppelmayr M, Hanslmayr S. Upper alpha ERD and absolute power: their meaning for memory performance. Prog Brain Res. 2006;159:151-65. Review.
Rivera J, González T. The Fibromyalgia Impact Questionnaire: a validated Spanish version to assess the health status in women with fibromyalgia. Clin Exp Rheumatol. 2004 Sep-Oct;22(5):554-60.

Responsible Party: Aragon Institute of Health Sciences
ClinicalTrials.gov Identifier: NCT01653457     History of Changes
Other Study ID Numbers: EC11-387
First Submitted: July 6, 2012
First Posted: July 31, 2012
Last Update Posted: July 31, 2012
Last Verified: July 2012

Keywords provided by Aragon Institute of Health Sciences:
Fibromyalgia
Magnetic Resonance Spectroscopy
Memantine
electroencephalic cordance

Additional relevant MeSH terms:
Fibromyalgia
Myofascial Pain Syndromes
Muscular Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Neuromuscular Diseases
Nervous System Diseases
Memantine
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents


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