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Trial registered on ANZCTR


Registration number
ACTRN12616001649404
Ethics application status
Approved
Date submitted
16/11/2016
Date registered
29/11/2016
Date last updated
5/03/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Correlation study of genetic variations with the pregabalin as analgesic in patients with chronic low back pain.
Scientific title
Correlation study of polymorphisms in genes SLC7A5 and SLC22A4 with the pregabalin efficacy and safety in patients with chronic low back pain.
Secondary ID [1] 290378 0
None
Universal Trial Number (UTN)
U1111-1189-0298
Trial acronym
CORPORAL

CORrelation study of POlymorphisms in genes SLC7A5 AND SLC22A4 with the pRegabalin efficAcy and safety in patients with chronic Low back pain
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic low back pain 300688 0
Condition category
Condition code
Anaesthesiology 300534 300534 0 0
Pain management

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients meeting the inclusion criteria will be informed of the purpose of the study and included in this after written consent which includes the consent to a blood sample for genomic testing.
Patients should make an initial assessment. During the initial assessment will assess pain intensity, functional impairment and sleep disturbance.
Thereafter patients should start their treatment, which reads as follows: The first week will take oral tablet Pregabalin dose to 25 mg twice daily followed by oral tablet Paracetamol at a dose of 1 gr twice daily. At the end of the week, patients will be assessed either in person or via telephone questionnaire. The parameters which will be evaluated by the pain intensity sleep quality, the functional impairment and the presence of serious side effects. Regarding side effects, we will first record the incidence of the most common of them, namely peripheral oedema,, dizziness, drowsiness, headache and fatigue, weight gain and dry mouth, horror, blurred vision and diplopias. At the same time these reactions will be evaluated and considered as serious on the basis of either the judgment of the therapist or the patient's discomfort as likely to require treatment discontinuation or dose reduction. If serious adverse reactions occur, patients should discontinue treatment with Pregabalin and will be excluded from the study.
Patients that will not appear any serious side effects will pass to the second phase of the study where the dosage of oral tablet pregabalin will be increased to 75 mg twice daily, followed by administering oral tablet paracetamol 1 g twice daily. Similarly those patients will be reassessed one week after starting this regimen for the parameters of the intensity of pain, function, sleep and side effects. If adverse effects occur that were not present in previous regimen, patients should return to this and reassess after 1 week.
In patients who will show improvement in the parameters of the intensity of pain, sleep and functionality (>10% reduction in pain and/or sleep and/or functionality scores from previous week), without presenting side effects, the dosage regimen will be increased to oral tablet pregabalin 225 mg daily (75 mg to morning and 150 mg in the evening) followed by oral tablet 1 g paracetamol twice daily, and will be reassessed after one week. If patients experience side effects they will return to the previous regimen and will be reassessed after one week.
In patients who show improvement (>10% reduction in pain and/or sleep and/or functionality scores from previous week) without the side effects dosage regimen will be increased to 150 mg twice daily (in combination with 1 g paracetamol twice daily). Similarly if they experience side effects they will return to the previous regimen.
In patients who show improvement in the parameters of the intensity of pain, sleep and functionality (>10% reduction in pain and/or sleep and/or functionality scores from previous week), without the side effects, the dosage regimen will be increased to oral tablet 450 mg daily (150 morning 300 evening), together with oral tablet 1 g paracetamol twice daily) and reassessed after one week. If they experience side effects they will return to the previous regimen and they will be reassessed after one week.
Finally, in patients who show improvement (10% reduction in pain and/or sleep and/or functionality scores from previous week) without the side effects regimen will increase to oral tablet 300 mg twice daily (in combination with oral tablet 1 g paracetamol twice daily). Similarly if they experience side effects they will return to the previous regimen.
Clinically significant result is the improvement of pain intensity, sleep and functionality evaluated with the questionnaire Low Back Pain Disability questionnaire at least 30% percent compared to baseline.
Patients' adherence to the treatment with pregabalin will be assessed by checking the empty drug packet return.
The total duration of each phase will be 7 days and the total duration of the intervention period will be 6 weekds (6 phases of 7 days each).
Intervention code [1] 296206 0
Treatment: Drugs
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 300220 0
Correlation of the total requirements for pregabalin (mg/kg/day) with SLC22A4 and SLC7A5 gene polymorphisms (assessed by serum assay).
Pregabalin total requirements will be assessed according to the prescribed therapy that every patient followed
Timepoint [1] 300220 0
Once a week during patients' therapy with pregabalin
Primary outcome [2] 300222 0
Correlation of gene polymorphisms with the subjective sensation of pain.
For the assessment of postoperative pain the NRS (Numerical Rating Scale) and BPI (Brief Pain Inventory) scales will be used.
Timepoint [2] 300222 0
Once a week during patients' therapy with pregabalin
Secondary outcome [1] 329423 0
Correlation of gene polymorphisms with sleep quality using the Pittsburgh Sleep Quality Index questionnaire (PSQI) and Epworth Sleepiness Scale (ESS)
Timepoint [1] 329423 0
Once a week during patients' therapy with pregabalin
Secondary outcome [2] 329425 0
Correlation of gene polymorphisms with functionality using the questionnaire Low Back Pain Disability Questionnaire
Timepoint [2] 329425 0
Once a week during patients' therapy with pregabalin
Secondary outcome [3] 329426 0
Correlation of the gene polymorphisms with their ability to tolerate the escalation in pregabalin treatment
The tolerance will be assesed with the adverse effects of pregabalin.
As adverse effects of pregabalin are considered patients clinical symptoms of peripheral oedema, dizziness, drowsiness, headache and fatigue, weight gain and dry mouth, blurred vision and diplopia
Timepoint [3] 329426 0
Once a week during patients' therapy with pregabalin
Secondary outcome [4] 329427 0
Correlation of the gene polymorphisms with the need for pregabalin discontinuation or dose reduction due to serious adverse events.
Adverse effects will be considered as serious on the basis of either the judgment of the therapist or the patient's discomfort.
Timepoint [4] 329427 0
Once a week during patients' therapy with pregabalin

Eligibility
Key inclusion criteria
1.Age 18-79 years
2.Patients with lumbar radicular pain for more than three months
3.Patients with disc prolapse, spinal stenosis or failed surgery in the lumbar spine
4.Patients with neuropathic pain which is certified both by the discovery of nerve damage points as weakness, numbness, hyperalgesia, allodynia and with a NRS score larger that 4/10.
Minimum age
18 Years
Maximum age
79 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Pain in the lumbar region stronger than the radicular pain
2. Significant motor deficits / disorders in urine bladder or bowel
3. Known depression with or without antidepressant treatment
4. Background of addiction or abuse
5. Current treatment with gabapentin, pregabalin or opioids
6. Diabetic or postherpetic neuropathy
7. Renal insufficiency, diabetes, congestive heart failure, thrombocytopenia.
8. Use of ACE inhibitors

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Participant recruitment difficulties
Date of first participant enrolment
Anticipated
15/12/2016
Actual
Date of last participant enrolment
Anticipated
1/12/2019
Actual
Date of last data collection
Anticipated
31/12/2019
Actual
Sample size
Target
200
Accrual to date
Final
Recruitment outside Australia
Country [1] 8399 0
Greece
State/province [1] 8399 0
Thessaloniki, Macedonia

Funding & Sponsors
Funding source category [1] 294995 0
University
Name [1] 294995 0
Aristotle University of Thessaloniki, Greece
Country [1] 294995 0
Greece
Primary sponsor type
University
Name
Aristotle University of Thessaloniki, Greece
Address
Aristotle University of Thessaloniki, University Campus, 54124, Thessaloniki, Greece
Country
Greece
Secondary sponsor category [1] 293813 0
None
Name [1] 293813 0
Address [1] 293813 0
Country [1] 293813 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296348 0
Scientific Committee of General University Hospital of Thessaloniki, AHEPA
Ethics committee address [1] 296348 0
Stilponos Kyriakidi 1, 54621, Thessaloniki, Greece
Ethics committee country [1] 296348 0
Greece
Date submitted for ethics approval [1] 296348 0
26/04/2016
Approval date [1] 296348 0
20/05/2016
Ethics approval number [1] 296348 0
323
Ethics committee name [2] 296349 0
Bioethics Committee of Medical School. Aristotle Univeristy of Thessaloniki, Greece
Ethics committee address [2] 296349 0
University Campus, 54124, Thessaloniki, Greece
Ethics committee country [2] 296349 0
Greece
Date submitted for ethics approval [2] 296349 0
09/05/2016
Approval date [2] 296349 0
06/07/2016
Ethics approval number [2] 296349 0
318

Summary
Brief summary
Genetic factors may alter the pharmacokinetic and pharmacodynamic properties of certain analgesic agents and therefore can modify individual clinical response to their administration. Although polymorphisms of enzymes responsible for the metabolism and transport of various drugs eventually affect their pharmacokinetics, other polymorphisms may also alter the pharmacodynamics of the particular drug. Patients with chronic low back pain have different requirements in analgesia. In order to investigate the possible association of the response of these patients to pregabalin with the polymorphisms of SLC6A4 and SLC7A5 genes we will administer pregabalin in an dose escalating timetable. Before treatment all patients will be assessed for subjective pain intensity, functional impairment and sleep disturbance. The pain intensity will be evaluated with the scales Numerical rating scale (NRS) and Brief Pain Inventory Scale (BPI). The sleep disorders will be assessed by the Pittsburgh Sleep Quality Index scale (PSQI) and Epworth Sleepiness Scale (ESS). The functional impairment will be assessed using the scale Roland Morris Low Back Pain Disability Questionnaire. The total pregabalin requirements as well as the drug effects in pain, sleep and fuctionality will be associated with the polymorphisms of SLC6A4 and SLC7A5 genes. Also the gene polymorphisms will be correlated with the presence of pregabalin serious adverse effects.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 1237 1237 0 0
/AnzctrAttachments/371703-Scientific Committee of AHEPA Hospital.pdf (Ethics approval)
Attachments [2] 1238 1238 0 0
/AnzctrAttachments/371703-Bioethics Committee.pdf (Ethics approval)

Contacts
Principal investigator
Name 69870 0
Dr Chryssa Pourzitaki
Address 69870 0
Department of Clinical Pharmacology, Faculty of Medicine, School of Health Sciences, University Campus, Aristotle University of Thessaloniki, 54124, Greece
Country 69870 0
Greece
Phone 69870 0
+302310999025
Fax 69870 0
+302310999312
Email 69870 0
[email protected]
Contact person for public queries
Name 69871 0
Maria Zouka
Address 69871 0
Clinic of Anesthesiology and Intensive Care, AHEPA University Hospital, Faculty of Medicine, School of Health Sciences, Stilponos Kyriakidi 1, Aristotle University of Thessaloniki, 54124, Greece
Country 69871 0
Greece
Phone 69871 0
+302313303743
Fax 69871 0
Email 69871 0
[email protected]
Contact person for scientific queries
Name 69872 0
Antonios Goulas
Address 69872 0
1st Department of Pharmacology, Faculty of Medicine, School of Health Sciences, University Campus, Aristotle University of Thessaloniki, 54124, Greece
Country 69872 0
Greece
Phone 69872 0
+302310999312
Fax 69872 0
+302310999312
Email 69872 0
[email protected]

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