Restless Legs SyndromePhase 1/2NCT00479154
Botulinum Toxin to Treat Restless Legs Syndrome
A Phase 1/2 study testing Botulinum Toxin A in people with Restless Legs Syndrome, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
This study will test whether botulinum toxin (Botox) may relieve the uncomfortable sensations patients with restless legs syndrome (RLS) experience. RLS is a common movement disorder that causes sensory discomfort and restlessness, most often in the legs, which improves with movement. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Restless Legs Syndrome
- What is being tested?
- Botulinum Toxin A
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- May 2007to Apr 2008
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 or older.
- Diagnosed with primary RLS based on presence of a characteristic clinical history and the International restless legs syndrome study group (IRLSSG) diagnostic criteria.
- A minimum score of 11 on the RLS rating scale (this is equivalent to a minimum rating of moderate severity).
- If subjects are on medications for RLS, the medication regimen must be stabilized for greater than 6 weeks prior to entering the study.
Who cannot join
- Subjects with any abnormal findings on neurological exam.
- Subjects with a dermatologic disorder that precludes injections in the legs.
- Subjects with a positive urine pregnancy test.
- Subjects without the capacity to give informed consent.
- Subjects taking aminoglycosides, chloroquine, clindamycin, hydroxychloroquine, magnesium sulfate, quinidine, or an anticoagulant.
- Subjects with abnormal clinical chemistry, hematology or urine drug screen by laboratory testing.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Pilot Study of Botulinum Toxin Type A for the Treatment of Restless Legs Syndrome
This study will test whether botulinum toxin (Botox) may relieve the uncomfortable sensations patients with restless legs syndrome (RLS) experience. RLS is a common movement disorder that causes sensory discomfort and restlessness, most often in the legs, which improves with movement. Although medications are available to treat the disorder, many people experience side effects that prevent them from continuing on the medication. The Food and Drug Administration has approved Botox for other movement disorders and for some cosmetic uses.
People 18 years of age or older with moderate to severe RLS who have been taking RLS medications for more than 6 weeks before entering the study may be eligible to participate. Candidates are screened with a medical history, physical and neurological examinations, blood tests and, for women who can become pregnant, a urine pregnancy test.
Read more
Participants are randomly assigned to receive injections of either Botox or placebo (salt water) into up to nine areas of the legs. The correct location of the muscles to be injected is determined by electromyography (EMG), a test that measures the electrical activity of muscles. For surface EMG, electrodes (small metal disks) are filled with a conductive gel and taped to the skin. Needle EMG involves inserting a needle into a muscle. Both methods are used in this study.
At 2 and 4 weeks after the injections, subjects are interviewed by telephone and asked to describe their symptoms, side effects and any improvement they may have noticed. After 12 weeks they return to NIH for injections with the alternate compound; that is, those who received Botox previously are given placebo for the second set of injections, and vice-versa. Subjects are again contacted by telephone 2 and 4 weeks after the injections to report their symptoms, side effects and benefits.
Read the detailed description
OBJECTIVE:
To evaluate the efficacy of botulinum toxin type A, (BoNT) for the treatment of primary Restless legs syndrome (RLS). We hypothesize that BoNT will be effective at decreasing the deep sensory discomfort of RLS.
STUDY POPULATION:
This protocol is a proof of principle double-blind randomized placebo-BoNT crossover outpatient pilot study of 6 patients diagnosed with moderate to very severe primary RLS.
DESIGN:
All subjects will be evaluated at the NIH Clinical Center by a study investigator to determine eligibility for participation in this protocol. We will obtain a complete medical history, and perform a neurological examination, along with laboratory screening studies. Subjects eligible to participate will receive baseline ratings using the Restless Legs Rating Scale (RLS-RS). Subjects will then be randomized to receive electromyography (EMG)-guided injections of up to 90 units of BoNT or an equivalent volume of saline in each lower extremity, in symptomatic muscles. Subjects will then receive follow up ratings at week 2 and 4 following each injection. Twelve weeks after receiving the first injection, subjects will crossover to receive the alternative compound with similar follow up ratings.
OUTCOME MEASURES:
The primary outcome measure will be mean change from baseline at 4 weeks post-injection on the RLS-RS for placebo and BoNT, while the other pre specified outcomes will evaluate patient reported Clinical Global Impression of Change (CGI-C) scores for each group, duration of effect, and adverse events. Only descriptive statistics will be performed on this limited data sample.
- Conditions
- Restless Legs Syndrome
- Being tested
- Botulinum Toxin A
- Keywords
- Restless Leg Syndrome, Botulinum Toxin, RLS
- Medical subject headings
- Restless Legs Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Botulinum Toxin ADrug
Also called onabotulinum toxin
Maximum dose of 90 units/leg was injected.
| Study group | Role | What they receive |
|---|---|---|
| Botulinum Toxin A | Experimental | Injection of onabotulinumtoxinA Receives: Drug: Botulinum Toxin A |
| Placebo (saline) | Placebo comparator | Injection of saline placebo Receives: Drug: Botulinum Toxin A |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Restless Legs Syndrome Rating Scale
Primary outcome measure will be the mean change from baseline in RLS scale at week 2 following placebo/BTX injections. Scoring criteria are: Mild (score 1-10); Moderate (score 11-20); Severe (score 21-30); Very severe (score 31-40).
Measured: Week 2 and Week 4 for each intervention (vs. baseline)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2007 (estimated)
- Study startMay 2007
- Primary completionApr 2008
- Study completionApr 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Restless Legs SyndromeStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Fatta Nahab, National Institutes of Health Clinical Center (CC)
- Investigators
- Fatta Nahab, MD, Principal investigator, NINDS/NIH
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00479154
- Sponsor's protocol ID
- 070160
- Other IDs
- 07-N-0160
- Status last verified
- Apr 2012
- First submitted
- 25 May 2007
- Last updated
- 26 Apr 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Blasi J, Chapman ER, Link E, Binz T, Yamasaki S, De Camilli P, Sudhof TC, Niemann H, Jahn R. Botulinum neurotoxin A selectively cleaves the synaptic protein SNAP-25. Nature. 1993 Sep 9;365(6442):160-3. doi: 10.1038/365160a0.
PubMed 8103915
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Botulinum Toxin Type A for the Treatment of Restless Legs Syndrome
- ClinicalTrials.gov ID
- NCT00479154
- Acronym / sponsor ID
- 070160
- Conditions
- Restless Legs Syndrome
- Keywords
- Restless Leg Syndrome, Botulinum Toxin, RLS
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 6 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- May 2007
- Primary completion
- Apr 2008 (actual)
- Study completion
- Apr 2008 (actual)
- First posted
- 28 May 2007 (estimated)
- Results
- Posted 26 Apr 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will test whether botulinum toxin (Botox) may relieve the uncomfortable sensations patients with restless legs syndrome (RLS) experience. RLS is a common movement disorder that causes sensory discomfort and restlessness, most often in the legs, which improves with movement. Although medications are available to treat the disorder, many people experience side effects that prevent them from continuing on the medication. The Food and Drug Administration has approved Botox for other movement disorders and for some cosmetic uses.
People 18 years of age or older with moderate to severe RLS who have been taking RLS medications for more than 6 weeks before entering the study may be eligible to participate. Candidates are screened with a medical history, physical and neurological examinations, blood tests and, for women who can become pregnant, a urine pregnancy test.
Participants are randomly assigned to receive injections of either Botox or placebo (salt water) into up to nine areas of the legs. The correct location of the muscles to be injected is determined by electromyography (EMG), a test that measures the electrical activity of muscles. For surface EMG, electrodes (small metal disks) are filled with a conductive gel and taped to the skin. Needle EMG involves inserting a needle into a muscle. Both methods are used in this study.
At 2 and 4 weeks after the injections, subjects are interviewed by telephone and asked to describe their symptoms, side effects and any improvement they may have noticed. After 12 weeks they return to NIH for injections with the alternate compound; that is, those who received Botox previously are given placebo for the second set of injections, and vice-versa. Subjects are again contacted by telephone 2 and 4 weeks after the injections to report their symptoms, side effects and benefits.
Detailed description
OBJECTIVE:
To evaluate the efficacy of botulinum toxin type A, (BoNT) for the treatment of primary Restless legs syndrome (RLS). We hypothesize that BoNT will be effective at decreasing the deep sensory discomfort of RLS.
STUDY POPULATION:
This protocol is a proof of principle double-blind randomized placebo-BoNT crossover outpatient pilot study of 6 patients diagnosed with moderate to very severe primary RLS.
DESIGN:
All subjects will be evaluated at the NIH Clinical Center by a study investigator to determine eligibility for participation in this protocol. We will obtain a complete medical history, and perform a neurological examination, along with laboratory screening studies. Subjects eligible to participate will receive baseline ratings using the Restless Legs Rating Scale (RLS-RS). Subjects will then be randomized to receive electromyography (EMG)-guided injections of up to 90 units of BoNT or an equivalent volume of saline in each lower extremity, in symptomatic muscles. Subjects will then receive follow up ratings at week 2 and 4 following each injection. Twelve weeks after receiving the first injection, subjects will crossover to receive the alternative compound with similar follow up ratings.
OUTCOME MEASURES:
The primary outcome measure will be mean change from baseline at 4 weeks post-injection on the RLS-RS for placebo and BoNT, while the other pre specified outcomes will evaluate patient reported Clinical Global Impression of Change (CGI-C) scores for each group, duration of effect, and adverse events. Only descriptive statistics will be performed on this limited data sample.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Botulinum Toxin A | Experimental | Drug: Botulinum Toxin AInjection of onabotulinumtoxinA |
| Placebo (saline) | Placebo comparator | Drug: Botulinum Toxin AInjection of saline placebo |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 18 or older.
- Diagnosed with primary RLS based on presence of a characteristic clinical history and the International restless legs syndrome study group (IRLSSG) diagnostic criteria.
- A minimum score of 11 on the RLS rating scale (this is equivalent to a minimum rating of moderate severity).
- If subjects are on medications for RLS, the medication regimen must be stabilized for greater than 6 weeks prior to entering the study.
Key exclusion criteria (6 listed)
- Subjects with any abnormal findings on neurological exam.
- Subjects with a dermatologic disorder that precludes injections in the legs.
- Subjects with a positive urine pregnancy test.
- Subjects without the capacity to give informed consent.
- Subjects taking aminoglycosides, chloroquine, clindamycin, hydroxychloroquine, magnesium sulfate, quinidine, or an anticoagulant.
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 AAlso: onabotulinum toxinMaximum dose of 90 units/leg was injected. | Drug | Botulinum Toxin A, Placebo (saline) |
Primary outcome
Change in Restless Legs Syndrome Rating Scale
Time frame: Week 2 and Week 4 for each intervention (vs. baseline)
Primary outcome measure will be the mean change from baseline in RLS scale at week 2 following placebo/BTX injections. Scoring criteria are: Mild (score 1-10); Moderate (score 11-20); Severe (score 21-30); Very severe (score 31-40).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 8103915Blasi J, Chapman ER, Link E, Binz T, Yamasaki S, De Camilli P, Sudhof TC, Niemann H, Jahn R. Botulinum neurotoxin A selectively cleaves the synaptic protein SNAP-25. Nature. 1993 Sep 9;365(6442):160-3. doi: 10.1038/365160a0.
Related trials for Restless Legs Syndrome
RecruitingObservational study
Lemborexant vs Clonidine vs Sedatives to Treat Insomnia in Chronic Pain Patients
Chronic Insomnia, Chronic Pain
Not yet recruiting
Neuromodulation to Overcome Severe Restless Legs Syndrome
Restless Leg Syndrome (RLS), Spinal Cord Stimulation (SCS)
Not yet recruitingPhase 2
Tolerability and Efficacy of CBD Extract for RLS Treatment
Restless Leg Syndrome
Recruiting
Functional Connectivity of the Interoceptive Network in RLS
Restless Legs Syndrome
Not yet recruitingPhase 2
Intravenous Iron in the Management of Drug-resistant Restless Legs syndromeI
Restless Legs Syndrome (RLS)
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.
Fatta Nahab, MD principal investigator
NINDS/NIH
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Botulinum Toxin A in people with Restless Legs Syndrome, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
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 4 inclusion and 6 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 26 Apr 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Yes. Results are posted in the registry (first posted 26 Apr 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Restless Legs Syndrome Rating Scale (time frame: Week 2 and Week 4 for each intervention (vs. baseline)). 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 NCT00479154, 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 26 Apr 2012.