Severe Refractory Neuropathic PainPhase 3SPIDOLNCT03942848
Intrathecal Ziconotide Antalgic Efficacy for Severe Refractory Neuropathic
A Phase 3 study of Severe Refractory Neuropathic Pain and Spinal Cord Lesions, run by Hospices Civils de Lyon.
Trial summary
Spinal cord injury (SCI) has an average prevalence of 50 per 100.000 in general population (30.000 patients with SCI in France) with estimates of the overall prevalence for severe neuropathic pain ranges from 30 to 51% (up to 10.000 patients in France). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Severe Refractory Neuropathic Pain, Spinal Cord Lesions
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- No sites listed yet
- Study dates
- 20 Jun 2019to 20 Sep 2021
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- • Patient > 18 year old
- Patients with stabilized spinal cord lesion
- Patients with refractory neuropathic pain with "Douleur Neuropathique" (DN4) score >4 at selection and failure at least of 2 classes of antineuropathic pain drugs alone or in association
- Experiences pain > 5/10 on numeric scale
- Patients with a positive trial test to Ziconotide either by lumbar puncture or by continuous infusion above the lesioned level via an implanted catheter
- Evaluation performed both by a multidisciplinary team in a pain center and a rehabilitation center
Show all 9Show fewer
- Patients eligible to surgical implantation of a subcutaneous pump
- Signed informed consent
- Patients benefiting from a social insurance system or a similar system
Who cannot join
- • Life expectancy < 5 years
- Suffering from other neuropathic pain or chronic pain due to cancer
- Being treated with spinal cord stimulation, nerve stimulation, intrathecal analgesic delivery system with analgesic drug (except Baclofen) until the last 6 months
- Implant ITZ surgery contraindication (MRI or anesthesia contraindication, coagulation disorder, Immunodepression, current infection, critical respiratory and/or heart illness)
- Unable to operate the ITZ equipment or comply with study requirements
- Suspicion of substance abuse
Show all 13Show fewer
- Current or planned pregnancy
- Patients with urinary tract disorder or urinary retention
- Patient under or planning to go under electromagnetic transcranial stimulation or planning to
- Patient unable to understand the purpose of the trial or refusing to follow treatment and post-treatment instructions
- Patients with history of psychiatric disorder or hallucination
- Participation to another trial that would interfere with this trial
- Patients under legal protection
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Assessment of Intrathecal Ziconotide Antalgic Efficacy for Severe Refractory Neuropathic Pain Due to Spinal Cord Lesions.
Spinal cord injury (SCI) has an average prevalence of 50 per 100.000 in general population (30.000 patients with SCI in France) with estimates of the overall prevalence for severe neuropathic pain ranges from 30 to 51% (up to 10.000 patients in France).
Patients with such spinal lesions may develop neuropathic pain called sublesional pain as perceived in an area below the level of injury. A second type of pain is at level of injury, i.e. perceived in a segmental pattern within the dermatome corresponding the spinal cord and nerve roots. These two types of pain are very harmful and are notoriously difficult to treat probably because of complex pathogenic mechanisms due to abnormal functioning of deafferented spinal and supraspinal nociceptive neurons.
Read more
Opioids, whatever be the route of administration, had demonstrated their inefficacy for these patients as well as several surgical techniques. So, chronic pain in relation with spinal lesion can be defined as real refractory pain.
Synaptic release of neurotransmitters is dependent on calcium intake trough voltage dependent channels. Type 2.1 or N-Type channels are specific for nociceptive system and can be blocked by a peptic neurotoxin: Ziconotide. Blocking these specific calcium channels neuromodulates nociception. Intrathecal use of Ziconotide, bringing the active molecule close to its receptors, has a proven clinical impact for a wide variety of pain (4). The intrathecal Ziconotide (ITZ) infusion using an implanted pump is validated for treatment of pain refractory to systemic analgesics (HAS, avis du 14-27 mai 2008). Meanwhile, no data are available in literature on positive effects of ITZ on specific spinal neuropathic pain.
A pilot study was performed by the coordinator team using ITZ on 12 patients with spinal pain: 8 patients had > 40% decrease of pain on numeric scale, 6 patients beneficiated from implanted pump allowing chronic ITZ treatment inducing 60% numeric scale decrease in average with 1 year follow-up.
Therefore intrathecal Ziconotide could be an excellent candidate for the treatment of spinal pain where the pain generators may be difficult to target by other available treatments.
This study is the first to assess ITZ (as IT antalgic monotherapy) versus placebo with a randomized controlled study with long follow-up. Trials have already been performed but not specially targeted spinal pain, and did not exceed three weeks follow-up.
Long term effects of Ziconotide on memory, cognition and mood have not been evaluated. In fact even though short term adverse effects on higher level functions have been described they have not been assessed in a placebo controlled situation.
Moreover, treating (successfully or not) patients with spinal pain could bring valuable insights both into the mechanisms of pain production in SCI patients and in the mechanisms of Ziconotide action: a positive result on pain below the injury level would imply action on the second or third order synapses of the nociceptive pathways. Similarly an effect at the level of pain, in absence of an effect below the level pain would argue discussion against such action. The impact of ITZ on the different clinical components of pain experienced by the patients, could also give some data on neuromodulation mechanism induced by the therapy.
- Being tested
- zicotinide followed by placebo, Placebo followed by zicotinide
- Keywords
- Spinal cord lesion, intrathecal infusion, refractory neuropathic pain, ziconotide
- Medical subject headings
- Neuralgia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
zicotinide followed by placeboDrug
The experimental treatment period consists of Ziconotide solution that will be prepared by each local pharmacy team, in 5 or 10 milliliter (ml) vials with constant concentration of 10micrograms/mL
Placebo followed by zicotinideDrug
The placebo treatment period consists in standard saline solution (preservative-free sodium chloride 9 milligram/milliliter (mg/ml) (0.9%) solution) which will be presented exactly in vials as presented for the treatment (volume, color, shape et size of the vial). Treating physicians will not be aware of the actual contents of the pump and will increase the volume of injected placebo as a treatment solution (as Ziconotide 10 micrograms/milliliter (μg/ml). The magnitude of increase is the decision of the treating physician (as long as it remains with the recommended limits by the Hospital Anxiety and Depression Scale (HAS) but most likely augmentations will be at maximum 1 microgram per month and maximum achieved doses allowed in SPIDOL study is 20 micrograms/day (in literature approximately 75% of patients who respond satisfactorily to treatment required a dose of ≤ 9.6 micrograms/day
| Study group | Role | What they receive |
|---|---|---|
| intrathecal Ziconotide followed by placebo | Experimental | Each of the 44 patients will receive alternatively treatment or placebo, for 6 months. The treatment for each period will be randomly assigned. A washout period of 15 days will be applied between the two periods of infusion. Receives: Drug: zicotinide followed by placebo; Drug: Placebo followed by zicotinide |
| intrathecal Ziconotide preceded by placebo | Placebo comparator | Each of the 44 patients will receive alternatively treatment or placebo, for 6 months. The treatment for each period will be randomly assigned. A washout period of 15 days will be applied between the two periods of infusion. Receives: Drug: zicotinide followed by placebo; Drug: Placebo followed by zicotinide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in pain between both treatment arms assessed by the Visual Analogic Scale (VAS)
The primary endpoint is the comparison, for each patient, of the mean pain intensity, within the last two week before the end of treatment, between two conditions: under Intrathecal Ziconotide (ITZ) and intrathecal (IT) placebo, using a visual analogic scale (VAS). This VAS is a graduated line from 0 to 10, 0 being the lowest level of pain and 10 being the highest level of pain.The final endpoint will be measured after 6 months of treatment and 6 months of placebo (or vice versa according to the random assignation of first treatment in this cross over design study), that is to say after a total of 12 months of treatment.
Measured: 12 months
Secondary outcomes (38)
Evaluation of Long term analgesic effect of intrathecal Ziconotide assessed by the Visual Analogic Scale (VAS)
Continuous evaluation of pain intensity will be assessed using a visual analogic scale during the 12 months of treatment. Pain intensity will be measured using visual analogic scale (VAS). This VAS is a graduated line from 0 to 10 with 0 being the lowest level of pain and 10 being the highest level of pain . The patient identifies his level of pain on this graduated line.
Measured: 12 months
Evaluation of Analgesic effect of at least 30%
Percentage of patients with at least 30% of pain reduction base on numeric scale within the last week before the end of treatment. Pain intensity will be measured using a visual analogic scale (VAS). This VAS is a graduated line from 0 to 10, 0 being the lowest level of pain and 10 being the highest level of pain. The patient identifies his level of pain on this graduated line.
Measured: 12 months
Evaluation of Severe Adverse Events (SAE)
Declaration of all severe adverse event occurring during the 12 months period of treatment. Each event will be analyzed by an independent committee to evaluate the immutability of the experimental treatment.
Measured: over the 12 months
Evaluation of patient satisfaction with pain treatment at first visit to refill the pump (1 month) assessed by the Visual Analogic Scale (VAS)
Satisfaction level of patient's pain relief will be assessed using a visual analogic scale (VAS). This VAS is a graduated line from 0 to 10, 0 being the lowest level of satisfaction and 10 being the highest satisfaction. The patient identifies his level of satisfaction of pain relief on this graduated line.
Measured: 1 month
Evaluation patient satisfaction of pain relief with the treatment at 6 months assessed by the Visual Analogic Scale (VAS)
Satisfaction level of patient's pain relief will be assessed using a visual analogic scale (VAS). This VAS is a graduated line from 0 to 10, 0 being the lowest level of satisfaction and 10 being the highest satisfaction. The patient identifies his level of satisfaction of pain relief on this graduated line.
Measured: 6 months
Evaluation patient satisfaction of pain relief with the treatment 12 months assessed by the Visual Analogic Scale (VAS)
Satisfaction level of patient's pain relief will be assessed using visual analogic scale (VAS). This VAS is a graduated line from 0 to 10, 0 being the lowest level of satisfaction and 10 being the highest satisfaction. The patient identifies his level of satisfaction of pain relief on this graduated line.
Measured: 12 months
Analgesic effect on spontaneous pain duration
Duration (average time per day)
Measured: 1 month before initiation of treatment
Analgesic effect on spontaneous pain duration
Duration (average time per day)
Measured: 6 months
Analgesic effect on spontaneous pain duration
Duration (average time per day)
Measured: 12 months
Analgesic effect on spontaneous pain intensity
Intensity of spontaneous pain will be assessed using a visual analogic scale (VAS). This VAS is a graduated line from 0 to 10, 0 being the lowest level of intensity of pain and 10 being the highest intensity of pain. The patient identifies his level of pain intensity on this graduated line.
Measured: 1 month before initiation of treatment
Analgesic effect on spontaneous pain intensity
intensity (numeric scale) of spontaneous pain. This numeric scale is a graduated line from 0 to 10, 0 being the lowest level of intensity of pain and 10 being the highest intensity of pain. T The patient identifies his level of pain intensity on this graduated line.
Measured: initial evaluation 6 months
Analgesic effect on spontaneous pain intensity
intensity (numeric scale) of spontaneous pain. This numeric scale is a graduated line from 0 to 10, 0 being the lowest level of pain intensity and 10 being the highest pain intensity. The patient identifies his level of pain intensity on this graduated line.
Measured: initial evaluation 12 months
Analgesic effect on provoked pain duration
Duration (average time per day)
Measured: initial evaluation
Analgesic effect on provoked pain duration
Duration (average time per day)
Measured: 6 months
Analgesic effect on provoked pain duration
Duration (average time per day)
Measured: 12 months
Analgesic effect on provoked pain intensity
Intensity of provoked pain will be assessed using a visual analogic scale (VAS). This VAS is a graduated line from 0 to 10, 0 being the lowest level of pain intensity and 10 being the highest pain intensity.
Measured: 1 month before initiation of treatment
Analgesic effect on provoked pain intensity
intensity of provoked pain will be assessed using a visual analogic scale (VAS). This VAS is a graduated line from 0 to 10, 0 being the lowest level of pain intensity and 10 being the highest pain intensity.
Measured: 6 months
Analgesic effect on provoked pain intensity
intensity of provoked pain will be assessed using a visual analogic scale (VAS). This VAS is a graduated line from 0 to 10, 0 being the lowest level of pain intensity and 10 being the highest pain intensity.
Measured: 12 months
Quality of life at inclusion assessed by the Short Form questionnaire (SF12)
Quality of life will be assessed using the 12 items Short Form questionnaire (SF12). It is a self-reported multipurpose questionnaire generic measure of health status. It measure in 12 questions, 8 concepts: physical functioning, role limitation due to physical health problems, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems and mental health. A specific algorithm gives a standardized total score between 0 and 100 for physical and mental summary scale. The higher the score, the better the quality of life.
Measured: 1 month before initiation of treatment
Quality of life at 6 months assessed by the Short Form questionnaire (SF12)
Quality of life will be assessed using the 12 items Short Form questionnaire (SF12). It is a self-reported multipurpose questionnaire generic measure of health status. It measure in 12 questions, 8 concepts: physical functioning, role limitation due to physical health problems, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems and mental health. A specific algorithm gives a standardized total score between 0 and 100 for physical and mental summary scale. The higher the score, the better the quality of life.
Measured: 6 months
Quality of life at 12 months assessed by the Short Form questionnaire (SF12)
Quality of life will be assessed using the 12 items Short Form questionnaire (SF12). It is a self-reported multipurpose questionnaire generic measure of health status. It measure in 12 questions, 8 concepts: physical functioning, role limitation due to physical health problems, bodily pain, general health, vitality, social functioning, role limitations due to emotional problems and mental health. A specific algorithm gives a standardized total score between 0 and 100 for physical and mental summary scale. The higher the score, the better the quality of life.
Measured: 12 months
Patient global impression of change
Patient global impression of change estimated using a using a visual analogic scale (VAS). This VAS is a graduated line from 0 to 10, 0 being the lowest level of pain intensity and 10 being the highest pain intensity.
Measured: at one months of treatment (first refill of the pump)
Patient global impression of change
Patient global impression of change estimated using a using a visual analogic scale (VAS). This VAS is a graduated line from 0 to 10, 0 being the lowest level of pain intensity and 10 being the highest pain intensity.
Measured: 6 months
Patient global impression of change
Patient global impression of change estimated using a visual analogic scale (VAS). This VAS is a graduated line from 0 to 10, 0 being the lowest level of pain intensity and 10 being the highest pain intensity.
Measured: 12 months
Analgesic drugs intake at inclusion
Quantification of analgesic drugs intake per day with differentiation of class of analgesics.
Measured: 1 month before initiation of treatment
Analgesic drugs intake at 12 months
Quantification of analgesic drugs intake per day with differentiation of class of analgesics.
Measured: 12 months
Evaluation of cognition effects induced by ITZ at inclusion
Mini Mental State Examination (MMSE) questionnaire will be used to evaluate cognition effect. Each 30 questions is one point. Patients with score greater than 27 has no mental issue, between 24 et 27 light dementia, less than 24 dementia.
Measured: 1 month before initiation of treatment
Evaluation of cognition effects induced by ITZ at 6 months
Mini Mental State Examination (MMSE) questionnaire will be used to evaluate cognition effect. Each 30 questions is one point. Patients with score greater than 27 has no mental issue, between 24 et 27 light dementia, less than 24 dementia.
Measured: 6 months
Evaluation of cognition effects induced by ITZ at 12 months
Mini Mental State Examination (MMSE) questionnaire will be used to evaluate cognition effect. Each 30 questions is one point. Patients with score greater than 27 has no mental issue, between 24 et 27 light dementia, less than 24 dementia.
Measured: 12 months
Measure of neuro- psychological effects of depression induced by ITZ
Hospital Anxiety and Depression Scale (HADS) for depression include 7 questions with a score from 0 to 3. If the score is greater than 11 then the patient suffer from depression
Measured: 1 month before initiation of treatment
Measure of neuro- psychological effects of depression induced by ITZ
Hospital Anxiety and Depression Scale (HADS) for depression include 7 questions with a score from 0 to 3. If the score is greater than 11 then the patient suffer from depression
Measured: 6 months
Measure of neuro- psychological effects of depression induced by ITZ
Hospital Anxiety and Depression Scale (HADS) for depression include 7 questions with a score from 0 to 3. If the score is greater than 11 then the patient suffer from depression
Measured: 12 months
Measure of neuro- psychological anxiety effects induced by ITZ
Hospital Anxiety and Depression Scale (HADS) for anxiety include 7 questions with a score from 0 to 3. If the score is greater than 11 then the patient suffer from anxiety.
Measured: 1 month before initiation of treatment
Measure of neuro- psychological anxiety effects induced by ITZ
Hospital Anxiety and Depression Scale (HADS) for anxiety include 7 questions with a score from 0 to 3. If the score is greater than 11 then the patient suffer from anxiety.
Measured: 6 months
Measure of neuro- psychological anxiety effects induced by ITZ
Hospital Anxiety and Depression Scale (HADS) for anxiety include 7 questions with a score from 0 to 3. If the score is greater than 11 then the patient suffer from anxiety.
Measured: 12 months
Impact of ITZ on psycho-social status of patients
Pain catastrophizing scale (PCS) score to assess the patient's physical and emotional distress associated with their pain condition. The scale is composed of 13 questions with a score for each questions going from 0 to 4. The final score is the addition of the score of each question, going from 0 to 52. Patient with a score greater than the 75% percentile mean value is at high risk of pain chronicity. Patient with a score between the 50 % and 75% percentile mean value is at moderate risk of pain chronicity
Measured: 1 month before initiation of treatment
Impact of ITZ on psycho-social status of patients
Pain catastrophizing scale (PCS) score to assess the patient's physical and emotional distress associated with their pain condition. The scale is composed of 13 questions with a score for each questions going from 0 to 4. The final score is the addition of the score of each question, going from 0 to 52. Patient with a score greater than the 75% percentile mean value is at high risk of pain chronicity. Patient with a score between the 50 % and 75% percentile mean value is at moderate risk of pain chronicity
Measured: 6 months
Impact of ITZ on psycho-social status of patients
Pain catastrophizing scale (PCS) score to assess the patient's physical and emotional distress associated with their pain condition. The scale is composed of 13 questions with a score for each questions going from 0 to 4. The final score is the addition of the score of each question, going from 0 to 52. Patient with a score greater than the 75% percentile mean value is at high risk of pain chronicity. Patient with a score between the 50 % and 75% percentile mean value is at moderate risk of pain chronicity
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2019
- Study start20 Jun 2019 (estimated)
- Primary completion20 Dec 2019 (estimated)
- Study completion20 Sep 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Severe Refractory Neuropathic PainStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 44 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- MERTENS Patrick, MD, PhD, Study director, Hospices Civils de Lyon
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03942848
- Sponsor's protocol ID
- 69HCL18_0034
- Acronym
- SPIDOL
- Status last verified
- May 2019
- First submitted
- 18 May 2018
- Last updated
- 8 May 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Intrathecal Ziconotide Antalgic Efficacy for Severe Refractory Neuropathic Pain Due to Spinal Cord Lesions.
- ClinicalTrials.gov ID
- NCT03942848
- Acronym / sponsor ID
- SPIDOL / 69HCL18_0034
- Keywords
- Spinal cord lesion, intrathecal infusion, refractory neuropathic pain, ziconotide
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 44 participants (estimated)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 20 Jun 2019 (estimated)
- Primary completion
- 20 Dec 2019 (estimated)
- Study completion
- 20 Sep 2021 (estimated)
- First posted
- 8 May 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Spinal cord injury (SCI) has an average prevalence of 50 per 100.000 in general population (30.000 patients with SCI in France) with estimates of the overall prevalence for severe neuropathic pain ranges from 30 to 51% (up to 10.000 patients in France).
Patients with such spinal lesions may develop neuropathic pain called sublesional pain as perceived in an area below the level of injury. A second type of pain is at level of injury, i.e. perceived in a segmental pattern within the dermatome corresponding the spinal cord and nerve roots. These two types of pain are very harmful and are notoriously difficult to treat probably because of complex pathogenic mechanisms due to abnormal functioning of deafferented spinal and supraspinal nociceptive neurons.
Opioids, whatever be the route of administration, had demonstrated their inefficacy for these patients as well as several surgical techniques. So, chronic pain in relation with spinal lesion can be defined as real refractory pain.
Synaptic release of neurotransmitters is dependent on calcium intake trough voltage dependent channels. Type 2.1 or N-Type channels are specific for nociceptive system and can be blocked by a peptic neurotoxin: Ziconotide. Blocking these specific calcium channels neuromodulates nociception. Intrathecal use of Ziconotide, bringing the active molecule close to its receptors, has a proven clinical impact for a wide variety of pain (4). The intrathecal Ziconotide (ITZ) infusion using an implanted pump is validated for treatment of pain refractory to systemic analgesics (HAS, avis du 14-27 mai 2008). Meanwhile, no data are available in literature on positive effects of ITZ on specific spinal neuropathic pain.
A pilot study was performed by the coordinator team using ITZ on 12 patients with spinal pain: 8 patients had > 40% decrease of pain on numeric scale, 6 patients beneficiated from implanted pump allowing chronic ITZ treatment inducing 60% numeric scale decrease in average with 1 year follow-up.
Therefore intrathecal Ziconotide could be an excellent candidate for the treatment of spinal pain where the pain generators may be difficult to target by other available treatments.
This study is the first to assess ITZ (as IT antalgic monotherapy) versus placebo with a randomized controlled study with long follow-up. Trials have already been performed but not specially targeted spinal pain, and did not exceed three weeks follow-up.
Long term effects of Ziconotide on memory, cognition and mood have not been evaluated. In fact even though short term adverse effects on higher level functions have been described they have not been assessed in a placebo controlled situation.
Moreover, treating (successfully or not) patients with spinal pain could bring valuable insights both into the mechanisms of pain production in SCI patients and in the mechanisms of Ziconotide action: a positive result on pain below the injury level would imply action on the second or third order synapses of the nociceptive pathways. Similarly an effect at the level of pain, in absence of an effect below the level pain would argue discussion against such action. The impact of ITZ on the different clinical components of pain experienced by the patients, could also give some data on neuromodulation mechanism induced by the therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| intrathecal Ziconotide followed by placebo | Experimental | Drug: zicotinide followed by placebo, Drug: Placebo followed by zicotinideEach of the 44 patients will receive alternatively treatment or placebo, for 6 months. The treatment for each period will be randomly assigned. A washout period of 15 days will be applied between the two periods of infusion. |
| intrathecal Ziconotide preceded by placebo | Placebo comparator | Drug: zicotinide followed by placebo, Drug: Placebo followed by zicotinideEach of the 44 patients will receive alternatively treatment or placebo, for 6 months. The treatment for each period will be randomly assigned. A washout period of 15 days will be applied between the two periods of infusion. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- • Patient > 18 year old
Key exclusion criteria (13 listed)
- • Life expectancy < 5 years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| zicotinide followed by placeboThe experimental treatment period consists of Ziconotide solution that will be prepared by each local pharmacy team, in 5 or 10 milliliter (ml) vials with constant concentration of 10micrograms/mL | Drug | intrathecal Ziconotide followed by placebo, intrathecal Ziconotide preceded by placebo |
| Placebo followed by zicotinideThe placebo treatment period consists in standard saline solution (preservative-free sodium chloride 9 milligram/milliliter (mg/ml) (0.9%) solution) which will be presented exactly in vials as presented for the treatment (volume, color, shape et size of the vial). Treating physicians will not be aware of the actual contents of the pump and will increase the volume of injected placebo as a treatment solution (as Ziconotide 10 micrograms/milliliter (μg/ml). The magnitude of increase is the decision of the treating physician (as long as it remains with the recommended limits by the Hospital Anxiety and Depression Scale (HAS) but most likely augmentations will be at maximum 1 microgram per month and maximum achieved doses allowed in SPIDOL study is 20 micrograms/day (in literature approximately 75% of patients who respond satisfactorily to treatment required a dose of ≤ 9.6 micrograms/day | Drug | intrathecal Ziconotide followed by placebo, intrathecal Ziconotide preceded by placebo |
Primary outcome
Change in pain between both treatment arms assessed by the Visual Analogic Scale (VAS)
Time frame: 12 months
The primary endpoint is the comparison, for each patient, of the mean pain intensity, within the last two week before the end of treatment, between two conditions: under Intrathecal Ziconotide (ITZ) and intrathecal (IT) placebo, using a visual analogic scale (VAS). This VAS is a graduated line from 0 to 10, 0 being the lowest level of pain and 10 being the highest level of pain.The final endpoint will be measured after 6 months of treatment and 6 months of placebo (or vice versa according to the random assignation of first treatment in this cross over design study), that is to say after a total of 12 months of treatment.
38 secondary outcomes
Evaluation of Long term analgesic effect of intrathecal Ziconotide assessed by the Visual Analogic Scale (VAS)
Time frame: 12 months
Evaluation of Analgesic effect of at least 30%
Time frame: 12 months
Evaluation of Severe Adverse Events (SAE)
Time frame: over the 12 months
Evaluation of patient satisfaction with pain treatment at first visit to refill the pump (1 month) assessed by the Visual Analogic Scale (VAS)
Time frame: 1 month
Evaluation patient satisfaction of pain relief with the treatment at 6 months assessed by the Visual Analogic Scale (VAS)
Time frame: 6 months
Evaluation patient satisfaction of pain relief with the treatment 12 months assessed by the Visual Analogic Scale (VAS)
Time frame: 12 months
Analgesic effect on spontaneous pain duration
Time frame: 1 month before initiation of treatment
Analgesic effect on spontaneous pain duration
Time frame: 6 months
Analgesic effect on spontaneous pain duration
Time frame: 12 months
Analgesic effect on spontaneous pain intensity
Time frame: 1 month before initiation of treatment
Analgesic effect on spontaneous pain intensity
Time frame: initial evaluation 6 months
Analgesic effect on spontaneous pain intensity
Time frame: initial evaluation 12 months
Analgesic effect on provoked pain duration
Time frame: initial evaluation
Analgesic effect on provoked pain duration
Time frame: 6 months
Analgesic effect on provoked pain duration
Time frame: 12 months
Analgesic effect on provoked pain intensity
Time frame: 1 month before initiation of treatment
Analgesic effect on provoked pain intensity
Time frame: 6 months
Analgesic effect on provoked pain intensity
Time frame: 12 months
Quality of life at inclusion assessed by the Short Form questionnaire (SF12)
Time frame: 1 month before initiation of treatment
Quality of life at 6 months assessed by the Short Form questionnaire (SF12)
Time frame: 6 months
Quality of life at 12 months assessed by the Short Form questionnaire (SF12)
Time frame: 12 months
Patient global impression of change
Time frame: at one months of treatment (first refill of the pump)
Patient global impression of change
Time frame: 6 months
Patient global impression of change
Time frame: 12 months
Analgesic drugs intake at inclusion
Time frame: 1 month before initiation of treatment
Analgesic drugs intake at 12 months
Time frame: 12 months
Evaluation of cognition effects induced by ITZ at inclusion
Time frame: 1 month before initiation of treatment
Evaluation of cognition effects induced by ITZ at 6 months
Time frame: 6 months
Evaluation of cognition effects induced by ITZ at 12 months
Time frame: 12 months
Measure of neuro- psychological effects of depression induced by ITZ
Time frame: 1 month before initiation of treatment
Measure of neuro- psychological effects of depression induced by ITZ
Time frame: 6 months
Measure of neuro- psychological effects of depression induced by ITZ
Time frame: 12 months
Measure of neuro- psychological anxiety effects induced by ITZ
Time frame: 1 month before initiation of treatment
Measure of neuro- psychological anxiety effects induced by ITZ
Time frame: 6 months
Measure of neuro- psychological anxiety effects induced by ITZ
Time frame: 12 months
Impact of ITZ on psycho-social status of patients
Time frame: 1 month before initiation of treatment
Impact of ITZ on psycho-social status of patients
Time frame: 6 months
Impact of ITZ on psycho-social status of patients
Time frame: 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 May 2019.
- Individual participant dataSharing planned: No
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MERTENS Patrick, MD, PhD study director
Hospices Civils de Lyon
Questions about this trial
What is this clinical trial studying?
A Phase 3 study of Severe Refractory Neuropathic Pain and Spinal Cord Lesions, run by Hospices Civils de Lyon.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 May 2019. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact MERTENS Patrick, MD, PhD (33 (0) 4 72 11 89 03, patrick.mertens@chu-lyon.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in pain between both treatment arms assessed by the Visual Analogic Scale (VAS) (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2019.