Botulinum Toxin for Cramps in Diabetic Neuropathy
Primary Purpose
Muscle Cramps Aggravated, Diabetes Mellitus
Status
Completed
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Botulinum toxin type A
Normal saline
Sponsored by
About this trial
This is an interventional treatment trial for Muscle Cramps Aggravated focused on measuring muscle cramps, diabetic neuropathy, botulinum toxin
Eligibility Criteria
Inclusion Criteria:
- accepting to participate to the study;
- age ≥ 45 and ≤ 75 years ;
- diabetes duration > 5 years and diabetic distal symmetric neuropathy present;
- stable glycemic control with last HbA1c value <9.0% (or 75 mmol/mol);
- cramps present at rest in either calf or foot muscles or both for at least 6 months;
- occurrence of cramps at least 3 times a week in the previous three months;
- previous unsuccessful or poorly tolerated pharmacological treatment with at least two of the following drugs: carbamazepine, quinine, phenytoin, magnesium supplements, and benzodiazepines.
Exclusion Criteria:
- the presence of other neurological diseases and of nephropathy, macro-angiopathy, cirrhosis, and lumbar disc diseases or the inability to give informed consent because of cognitive impairment.
- Patients previously treated with BoNT/A for any reason were also excluded
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
botulinum toxin type A
Normal saline
Arm Description
Botulinum toxin type A (100 or 30 units) was injected for each side into the gastrocnemious or the small flexor foot muscles, respectively, according to the predominance of leg or foot cramps.
The same dosage as the active group, but with normal saline alone were injected into the gastrocnemious or the small flexor foot muscles, respectively, according to the predominance of leg or foot cramps.
Outcomes
Primary Outcome Measures
pain intensity on a 0-10 severity scale
the intensity of pain was rated on a scale 0 to 10, with 0 indicating no pain and 10 indicating "the worst pain imaginable"
Secondary Outcome Measures
cramp frequency
the changes in cramp frequency, the Cramp Severity Scale (CSS) were evaluated over the course of 20 weeks after BoNT/A administration
the Cramp Severity Scale (CSS)
the changes in the Cramp Severity Scale (CSS) were evaluated over the course of 20 weeks after BoNT/A administration
the Cramp Threshold Frequency (CTF)
the changes in the Cramp Threshold Frequency were evaluated over the course of 20 weeks after BoNT/A administration
Full Information
NCT ID
NCT03238898
First Posted
June 9, 2017
Last Updated
August 2, 2017
Sponsor
Presidio Ospedaliero Garibaldi-Centro
1. Study Identification
Unique Protocol Identification Number
NCT03238898
Brief Title
Botulinum Toxin for Cramps in Diabetic Neuropathy
Official Title
Botulinum Toxin for Muscle Cramps in Diabetic Patients With Diabetic Neuropathy
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
September 27, 2014 (Actual)
Primary Completion Date
May 3, 2017 (Actual)
Study Completion Date
May 3, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Presidio Ospedaliero Garibaldi-Centro
4. Oversight
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Objective: previous studies suggest that botulinum toxin A (BoNT/A) can reduce muscle hyperactivity.
Research Design and Methods: a single-center, double-blind and placebo-controlled study investigating the efficacy and safety of BoNT/A intramuscular injection for treating calf or foot cramps refractory to common pharmacological drugs in patients with diabetic peripheral neuropathy. Fifty patients were subdivided in two matched groups (cases and controls) and BoNT/A (100 or 30 units) was injected for each side into the gastrocnemious or the small flexor foot muscles, respectively, according to the predominance of leg or foot cramps. Responders were evaluated again with a second BoNT/A administration.
The changes of pain intensity (primary outcome) and the changes in cramp frequency, the and the Cramp Severity Scale (CSS) were evaluated over the course of 20 weeks after BoNT/A administration.
Detailed Description
This was a single-center, randomized, double-blind, placebo-controlled prospective study.
A consecutive series of 303 out-patients with type 2 diabetes was screened for muscle cramps.Patients were asked to report in a questionnaire the frequency, localization, intensity and time of the day of cramps. Out of these 303 diabetic patients with cramps, fifty patients satisfied the inclusion/exclusion criteria and entered the study.
Cramp Evaluation
a) Clinical evaluation All patients completed a baseline diary in the week before treatment. Every day the number of muscle cramp episodes was reported three times a day and the intensity of pain was rated on a scale 0 to 10, with 0 indicating no pain and 10 indicating "the worst pain imaginable" (Brief Pain Inventory-Modified Short Form, BPI-MSF, point 1). Daily data in this pre-treatment week were averaged and considered "basal" values. A similar daily diary, reporting the number of pain episodes, their intensity, time of the day and duration (less or more than 1 min) was kept throughout the study for the three days before each control visit.
The severity of cramps interference on daily life was graded according to the functional scale Cramp Severity Score (CSS): 0= no cramps; 1= occasional day or night cramps not interfering with daily activities or with nocturnal sleep; 2= frequent muscle cramps triggered by muscle exercise not significantly interfering with daily activity or with nocturnal sleep; 3= continuous or subcontinuous muscle cramps limiting daily activities or nocturnal sleep; 4= continuous cramps severely interfering with daily activities and nocturnal sleep (4).
Randomisation: patients were randomly assigned to either the treatment or control groups according to a computer-generated list. Randomization was stratified in order to match age, gender, duration of diabetes and the frequency and severity of cramp episodes in the two groups.
At time 0 each patient received four i.m. injections, two injections for each side, containing either BoNT/A (100 units diluted in 1 ml saline) or saline. The total dose, for each side, was 100 units for the gastrocnemius muscle or 30 units for the small flexor foot muscles. The calf or the foot muscles were chosen according to the patient predominant leg or foot cramps. Patients in the control group received the same volumes of normal saline in the same muscles. The injections were prepared by a research nurse and both the treating physician and the patients were left blind.
Ten visits were scheduled after initial evaluation: at weeks 1 and 2 after BoNT/A injection and, thereafter, every other week until week 16 and then at week 20. Ratings of the three days before each control visit were averaged to obtain values for each post-injection evaluation. The number of cramp episodes and cramp severity score (both self-reported in the daily diary) were obtained at 1, 4, 8, 12, 16 and 20 weeks after BoNT/A or placebo administration.
Positive response to treatment: a 30% or greater reduction of the primary outcome score.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscle Cramps Aggravated, Diabetes Mellitus
Keywords
muscle cramps, diabetic neuropathy, botulinum toxin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Model Description
randomized, double-blind and placebo-controlled study
Masking
Participant
Masking Description
double-blind
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
botulinum toxin type A
Arm Type
Active Comparator
Arm Description
Botulinum toxin type A (100 or 30 units) was injected for each side into the gastrocnemious or the small flexor foot muscles, respectively, according to the predominance of leg or foot cramps.
Arm Title
Normal saline
Arm Type
Placebo Comparator
Arm Description
The same dosage as the active group, but with normal saline alone were injected into the gastrocnemious or the small flexor foot muscles, respectively, according to the predominance of leg or foot cramps.
Intervention Type
Drug
Intervention Name(s)
Botulinum toxin type A
Intervention Description
botulinum toxin type A injections
Botulinum toxin type A (100 or 30 units) was injected for each side into the gastrocnemious or the small flexor foot muscles, respectively, according to the predominance of leg or foot cramps.
Intervention Type
Other
Intervention Name(s)
Normal saline
Other Intervention Name(s)
Placebo
Intervention Description
Normal saline injections
The same dosage as the active group, but with normal saline alone were injected into the gastrocnemious or the small flexor foot muscles, respectively, according to the predominance of leg or foot cramps.
Primary Outcome Measure Information:
Title
pain intensity on a 0-10 severity scale
Description
the intensity of pain was rated on a scale 0 to 10, with 0 indicating no pain and 10 indicating "the worst pain imaginable"
Time Frame
20 weeks
Secondary Outcome Measure Information:
Title
cramp frequency
Description
the changes in cramp frequency, the Cramp Severity Scale (CSS) were evaluated over the course of 20 weeks after BoNT/A administration
Time Frame
20 weeks
Title
the Cramp Severity Scale (CSS)
Description
the changes in the Cramp Severity Scale (CSS) were evaluated over the course of 20 weeks after BoNT/A administration
Time Frame
20 weeks
Title
the Cramp Threshold Frequency (CTF)
Description
the changes in the Cramp Threshold Frequency were evaluated over the course of 20 weeks after BoNT/A administration
Time Frame
20 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
accepting to participate to the study;
age ≥ 45 and ≤ 75 years ;
diabetes duration > 5 years and diabetic distal symmetric neuropathy present;
stable glycemic control with last HbA1c value <9.0% (or 75 mmol/mol);
cramps present at rest in either calf or foot muscles or both for at least 6 months;
occurrence of cramps at least 3 times a week in the previous three months;
previous unsuccessful or poorly tolerated pharmacological treatment with at least two of the following drugs: carbamazepine, quinine, phenytoin, magnesium supplements, and benzodiazepines.
Exclusion Criteria:
the presence of other neurological diseases and of nephropathy, macro-angiopathy, cirrhosis, and lumbar disc diseases or the inability to give informed consent because of cognitive impairment.
Patients previously treated with BoNT/A for any reason were also excluded
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
9029067
Citation
Bertolasi L, Priori A, Tomelleri G, Bongiovanni LG, Fincati E, Simonati A, De Grandis D, Rizzuto N. Botulinum toxin treatment of muscle cramps: a clinical and neurophysiological study. Ann Neurol. 1997 Feb;41(2):181-6. doi: 10.1002/ana.410410209.
Results Reference
result
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Botulinum Toxin for Cramps in Diabetic Neuropathy
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