The primary objective of this study is to investigate whether SCS combined with best (drug) treatment as usual (TAU) leads to clinically significant (>=50%) pain relief in patients suffering from moderate-to-severe PDP in the lower limbs after 6…
ID
Source
Brief title
Condition
- Diabetic complications
- Peripheral neuropathies
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The main study parameter will be the mean pain intensity during daytime and/or
mean pain intensity during night time as measured on a weighted NRS and/or a
PGIC for pain and sleep measured on a 7-point Likert scale.
Secondary outcome
1) Quality of life will be measured by EQ-5D, MOS SF-36 and the modified BPI
Short Form for diabetic peripheral neuropathy;
2) Quality of sleep will be measured by the MOS sleep scale;
3) The effect of SCS on mood will be measured by the BDI;
4) The effect of SCS on blood glucose control will be investigated by measuring
HbA1c;
5) To measure the effect of SCS on large and small neurofibre functions the
modified INCAT sensory sum score (md ISS), Contact Heat Evoked Potentials
Stimulator (CHEPS), and Somato-sensory evoked potentials (SSEP) measurements
will be performed;
6) The effect of SCS on small fibre loss and possible regeneration will be
investigated by skin biopsy;
7) The effect of SCS on activities-of-daily-living will be measured with an
accelerometer (activPALTM);
8) All baseline parameters will be analyzed for their predictive value for the
success or failure of SCS treatment in PDP; e.g. pain scores, NPS, EuroQol-5D,
MOS SF-36, BDI, Michigan Diabetic Neuropathy Score (MDNS) , md INCAT sensory
sum score, CHEPS, SSEP, HbA1c and skin biopsy;
9) Costs will be measured through the hospital registration and by means of a
standardized cost-questionnaire and the EQ-5D;
10) The long term follow-up will measured for 5 years, twice each year, by
using the same questionnaire and pain dairy.
Background summary
Diabetic neuropathy is one of the most common complications of Diabetes Melitus
(DM). Pain is a frequent symptom of diabetic neuropathy. The prevalence of pain
in diabetes patients is estimated between 11-34%. Painful diabetic
polyneuropathy (PDP) is a problem with a large societal and economic impact due
to the high prevalence of DM and the large impact of PDN on quality of life and
daily functioning of patients. Until ths moment no effective treatment of PDP
is available. A large portion of patients experience unacceptable pain despite
maximal drug therapy. For this patients spinal cord stimulation (SCS) may be
able to provide pain relief. SCS had been used for over 30 years now for a
diversity of neuropathic pain states. Due to this large experience SCS is a
safe technique. Percutaneous implantation of the lead is a minimally invasive
procedure with a low risk of infection.
Study objective
The primary objective of this study is to investigate whether SCS combined with
best (drug) treatment as usual (TAU) leads to clinically significant (>=50%)
pain relief in patients suffering from moderate-to-severe PDP in the lower
limbs after 6 months of treatment compared to best (drug) treatment as usual.
Secondary objectives to investigate after 6 months:
1) the effect of SCS on health related quality of life in PDP;
2) the effect of SCS on the quality of sleep in PDP;
3) the effect of SCS on mood in PDP;
4) the effect of SCS on blood glucose control in PDP;
5) the effect of SCS on large and small nerve fibre functions in PDP;
6) identifying predictive factors for success of SCS treatment of PDP;
7) the effect of SCS on activities-of-daily-living;
Secondary objectives to investigate after 12 months:
8) the effect of SCS on small fibre loss and regeneration in PDP (only in group
1);
9) costs, cost-utility and cost-effectiveness
Study design
The study design is a multi centre randomized controlled trial. Patients will
be randomized at random into 2 groups. The first group will be treated with SCS
in addition to best (drug) treatment as usual. The second group will receive
best (drug) treatment as usual without SCS. Patients will be included following
the in- and exclusion criteria and follow the treatment algorithm as showed
below.
Group 1: the effect of SCS will be analyzed after 2 weeks of trial stimulation.
Patient will receive a definitive SCS system if they meet the above mentioned
criteria. The patients will be followed during 12 moths at timepoints
baseline, 3, 6, 9 and 12 months.
Group 2: receives best (drug) treatment as usual (standard treatment) en will
be followed during 6 months. Timepoint will be baseline, 3 and 6 months.
Intervention
The intervention is spinal cord stimulation.
Study burden and risks
Risks:
Technical adverse events:
- Lead migration (14%
- Lead breakage (7%)
- Implanted pulse generator migration (1%)
- Loss of therapeutic effect, lost or unpleasant paresthesias (12%)
Medical adverse events:
- Infection or wound breakdown (10%)
- Pain at IPG incision site (12%)
- IPG pocket fluid collection (5%)
The lead will be implanted in the operating theatre under local anesthesia
using a percutaneous technique with a Tuohy needle. The pulse generator will be
implanted subcutaneously under general anesthesia.
Nature of burden cosist of:
- filling out quenstionannaires and investigations.
- group 1: total time investment 20.5 hours spread over 1 year
- group 2: total time investment 11 hours spread over 6 months
- the implantation of the lead and pulse generatir will be in total 3 hours.
This only contains group 1 and is already included in the total time of 20.5
hours.
P. Debyelaan 25
6229 HX Maastricht
NL
P. Debyelaan 25
6229 HX Maastricht
NL
Listed location countries
Age
Inclusion criteria
• Moderate-to-severe PDP in the lower limbs
o The pain intended to treat has been present for more than 12 months
o Previous treatment has been unsuccessful (insufficient pain relief and/or unacceptable side-effects) with drugs from the following drug categories:
* Amitriptylin or an other tricyclic antidepressant and/or
* Pregabalin (Lyrica®) or Gabapentin (Neurontin®) and/or
* Duloxetine (Cymbalta®) and/or
* Tramadol or strong opioids
Patients were treated with 3 drugs from the above mentioned drug categories and followed the treatment algorithm for painful diabetic polyneuropathy according to Jensen. Starting dosage was based on individual patient characteristics. Each drug was tried for at least 3 weeks and dose was raised once, if possible. By insufficient pain relief and/or unacceptable side-effects, the drug treatment was stopped. Patients reached a steady state in medication use and it is not allowed to increase dosage during the study. Use of opioids during the study is not allowed.
• Mean pain intensity during daytime and/or night time should be 5 or higher measured on a numeric rating scale (NRS). Pain during daytime will be scored 3 times per day during for 4 days according to Jensen.
• Patient*s age is between 18 and 80 years.
• It is necessary that patients which use anti coagulation, especially coumarin derivatives, can stop for 10 days around the procedure. This will be authorized by the treating physician of the patient. There will be no bridging to heparin.
Exclusion criteria
• The patient has had neuromodulation therapy during the month before the intake
• Neuropathic pain is most prevalent in the upper limbs (NRS>3)
• Neuropathy or chronic pain of other origin than diabetes mellitus (NRS> 3)
• Use of opioids
• Addiction: drugs, alcohol (> 5E / day) and/or medication
o Drugs: cocaine, heroine, marihuana.
o Alcohol: wine, beer, liquor (max 5E / day)
o Medication: benzodiazepines.
• Insufficient cooperation from the patient (little motivation, understanding or communication)
• Blood clotting disorder
• Immune deficiency (HIV-positive, corticosteroids with a dose equivalent to > prednisolone 10 mg, immunodepressiva, etc.)
• Peripheral vascular disease without palpable peripheral pulses at both feet (inclusion is possible if pulses are absent, but ankle brachial index is between 0.7 and 1.2 in both feet)
• Active foot ulceration
• Life expectancy < 1 year
• Pacemaker
• Local infection or other skin disorders at site of incision
• Psychiatric problems potentially interfering with cooperation in the study
• Pregnancy
• Severe cardiac or pulmonary failure (> NYHA classification II)
• Unstable blood glucose control (change in HbA1c>1,0% in three months prior to inclusion)
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL30961.068.09 |