Clinical Trials Logo

Clinical Trial Details — Status: Not yet recruiting

Administrative data

NCT number NCT01653457
Other study ID # EC11-387
Secondary ID
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


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)

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. — View Citation

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. — View Citation

Briley M. Drugs to treat fibromyalgia - the transatlantic difference. Curr Opin Investig Drugs. 2010 Jan;11(1):16-8. — View Citation

Chen HS, Lipton SA. The chemical biology of clinically tolerated NMDA receptor antagonists. J Neurochem. 2006 Jun;97(6):1611-26. Review. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 31 references in allClick 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
See also
  Status Clinical Trial Phase
Active, not recruiting NCT05659862 - Digitally Assisted Behavioral Physical Activity Intervention in Fibromyalgia N/A
Recruiting NCT03207828 - Testing Interventions for Patients With Fibromyalgia and Depression N/A
Completed NCT03042728 - Impact of Inclusion of a Therapy Dog Visit as Part of the Fibromyalgia Treatment Program N/A
Recruiting NCT06097091 - Effects and Mechanisms of Pain Neuroscience Education in Patients With Fibromyalgia N/A
Recruiting NCT04554784 - Effectiveness of Bowen Therapy for Pain Management in Patients With Fibromyalgia N/A
Completed NCT03300635 - Metabolism, Muscle Function and Psychological Factors in Fibromyalgia N/A
Recruiting NCT06166563 - Exercise, Irritable Bowel Syndrome and Fibromyalgia N/A
Completed NCT03166995 - Postural Exercises in Women With Fibromyalgia N/A
Completed NCT03227952 - Sensory Stimulation in Fibromyalgia N/A
Recruiting NCT06237595 - Vagus Nerve Stimulation in Fibromyalgia N/A
Completed NCT01888640 - Fibromyalgia Activity Study With Transcutaneous Electrical Nerve Stimulation (FAST) N/A
Completed NCT03641495 - Pain Education and Therapeutic Exercise for Fibromyalgia N/A
Recruiting NCT05581628 - FREQUENCY OF FIBROMYALGIA IN PATIENTS WITH CELIAC DISEASE
Active, not recruiting NCT05128162 - Open-label Study to Assess the Safety and Efficacy of Psilocybin With Psychotherapy in Adult Participants With Fibromyalgia Phase 2
Completed NCT04674878 - Comparison of Muscle Energy Techniques and Breathing Exercises for Functional Improvement in Fibromyalgia N/A
Active, not recruiting NCT04084795 - Augmentation of EMDR With tDCS in the Treatment of Fibromyalgia N/A
Completed NCT03129906 - Impact of the Restriction of Sources of Gluten in Fibromyalgia Patients N/A
Completed NCT05058911 - Exposure-based Cognitive Behavior Therapy vs Traditional Cognitive Behavior Therapy for Fibromyalgia N/A
Recruiting NCT04571528 - Effectiveness of VIRTUAL FIBROWALK STUDY N/A
Recruiting NCT04571853 - New Educational Tool for FM N/A