Muscle Cramps AggravatedPhase 2NCT03238898
Botulinum Toxin for Cramps in Diabetic Neuropathy
A Phase 2 study testing Botulinum toxin type A and Normal saline in people with Muscle Cramps Aggravated and Diabetes Mellitus, run by Presidio Ospedaliero Garibaldi-Centro.
Trial 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… Read more about this study
- Who is it for?
- Ages 45 to 75 years
- Conditions the study is for
- Muscle Cramps Aggravated, Diabetes Mellitus
- What is being tested?
- Botulinum toxin type A and Normal saline
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- No sites listed yet
- Study dates
- 27 Sep 2014to 3 May 2017
- Phase
- Phase 2
- 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 45 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
About this study
Official title: Botulinum Toxin for Muscle Cramps in Diabetic Patients With Diabetic Neuropathy
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.
Read the 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
- 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.
- Conditions
- Muscle Cramps Aggravated, Diabetes Mellitus
- Being tested
- Botulinum toxin type A, Normal saline
- Keywords
- muscle cramps, diabetic neuropathy, botulinum toxin
- Medical subject headings
- Diabetes Mellitus, Muscle Cramp, Diabetic Neuropathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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.
Normal salineOther
Also called Placebo
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.
| Study group | Role | What they receive |
|---|---|---|
| botulinum toxin type A | Active comparator | 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. Receives: Drug: Botulinum toxin type A |
| Normal saline | Placebo comparator | 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. Receives: Other: Normal saline |
What is being measured
The primary outcome is the main question the study is designed to answer.
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"
Measured: 20 weeks
Secondary outcomes (3)
cramp frequency
the changes in cramp frequency, the Cramp Severity Scale (CSS) were evaluated over the course of 20 weeks after BoNT/A administration
Measured: 20 weeks
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
Measured: 20 weeks
the Cramp Threshold Frequency (CTF)
the changes in the Cramp Threshold Frequency were evaluated over the course of 20 weeks after BoNT/A administration
Measured: 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2017
- Study start27 Sep 2014
- Primary completion3 May 2017
- Study completion3 May 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Muscle Cramps AggravatedStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- randomized, double-blind and placebo-controlled study
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 50 participants (actual)
Sponsor and investigators
- Lead sponsor
- Presidio Ospedaliero Garibaldi-Centro
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Domenico Antonio Restivo, Presidio Ospedaliero Garibaldi-Centro
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03238898
- Sponsor's protocol ID
- btx for cramps
- Status last verified
- Aug 2017
- First submitted
- 9 Jun 2017
- Last updated
- 3 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 9029067
Study at a glance
From the registry record, last updated by the sponsor on 3 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Botulinum Toxin for Muscle Cramps in Diabetic Patients With Diabetic Neuropathy
- ClinicalTrials.gov ID
- NCT03238898
- Acronym / sponsor ID
- btx for cramps
- Conditions
- Muscle Cramps Aggravated, Diabetes Mellitus
- Keywords
- muscle cramps, diabetic neuropathy, botulinum toxin
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 50 participants (actual)
- Lead sponsor
- Presidio Ospedaliero Garibaldi-CentroUniversity, hospital or other
- Study start
- 27 Sep 2014 (actual)
- Primary completion
- 3 May 2017 (actual)
- Study completion
- 3 May 2017 (actual)
- First posted
- 3 Aug 2017 (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.
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
- 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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- randomized, double-blind and placebo-controlled study
| Arm | Type | Receives |
|---|---|---|
| botulinum toxin type A | Active comparator | Drug: Botulinum toxin type ABotulinum 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. |
| Normal saline | Placebo comparator | Other: Normal salineThe 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. |
Who may qualify
- Ages
- 45 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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;
Key exclusion criteria (2 listed)
- 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
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 |
|---|---|---|
| Botulinum toxin type Abotulinum 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. | Drug | botulinum toxin type A |
| Normal salineAlso: PlaceboNormal 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. | Other | Normal saline |
Primary outcome
pain intensity on a 0-10 severity scale
Time frame: 20 weeks
the intensity of pain was rated on a scale 0 to 10, with 0 indicating no pain and 10 indicating "the worst pain imaginable"
3 secondary outcomes
cramp frequency
Time frame: 20 weeks
the Cramp Severity Scale (CSS)
Time frame: 20 weeks
the Cramp Threshold Frequency (CTF)
Time frame: 20 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Aug 2017.
- Results publication: PubMed 9029067Bertolasi 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.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Botulinum toxin type A and Normal saline in people with Muscle Cramps Aggravated and Diabetes Mellitus, run by Presidio Ospedaliero Garibaldi-Centro.
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 7 inclusion and 2 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: finished, as of the sponsor's last update on 3 Aug 2017. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
pain intensity on a 0-10 severity scale (time frame: 20 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03238898, which also lists 1 linked publication.
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 3 Aug 2017.