Andersen-Tawil SyndromePhase 1NCT00839501
Effect of Potassium and Acetazolamide on People With Andersen-Tawil Syndrome
A Phase 1 study testing Potassium and Acetazolamide in people with Andersen-Tawil Syndrome, run by University of Rochester at 1 site in United States.
Trial summary
Andersen-Tawil Syndrome (ATS) is a rare genetic disorder that causes episodes of muscle weakness, potentially life-threatening changes in heart rhythm, and skeletal developmental abnormalities. The cause of some ATS cases remains unknown, and no specific treatments have been established. Read more about this study
- Who is it for?
- Ages 10 years and older
- Conditions the study is for
- Andersen-Tawil Syndrome
- What is being tested?
- Potassium and Acetazolamide
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2008to Jan 2011
- Phase
- Phase 1
- 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 10 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Clinically confirmed diagnosis of Andersen-Tawil Syndrome, as defined by at least two of the following three features:
- Neuromuscular Feature
- Presence of clear-cut episodes of transient muscle weakness with or without a fixed deficit that is typical with rest after exertion or prolonged rest, OR
- An atypical history with specific exam findings (absent reflexes with normal sensation ictally), OR
- Unexplained intraictal hypokalemia, OR
- An abnormal nerve conduction exercise test
Show all 21Show fewer
- Cardiac Feature
- Prolonged QTc interval on 12-lead electrocardiogram (ECG), according to standard criteria, AND/OR
- Ventricular ectopy, including uniform or multifocal PVCs, polymorphic VT, or bidirectional VT
- Physical Feature (at least two of the below five features)
- Low set ears
- Hypertelorism
- Small mandible
- Clinodactyly
- Syndactyly
- Micromelia of hands or feet
- -OR-
- One of the three above criteria, with at leat one other family member meeting two criteria
- -OR-
- Not meeting clinical criteria but possessing the KCNJ2 mutation
- An average frequency of at least one neuromuscular symptom (attack of weakness) per week
Who cannot join
- Sulfa allergy
- Renal impairment, as defined by serum creatine greater than 1.5 mg/dl
- History of renal calculi
- Cardiac disease or other disease that would make potassium supplementation or acetazolamide treatment inadvisable
- Diabetes mellitus
- Currently taking quinidine
- Pregnant
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Rochester School of Medicine
Rochester, New York, 14642
About this study
Official title: Therapeutic Trial of Potassium and Acetazolamide in Andersen-Tawil Syndrome
Andersen-Tawil Syndrome (ATS) is a rare genetic disorder that causes episodes of muscle weakness, potentially life-threatening changes in heart rhythm, and skeletal developmental abnormalities. The cause of some ATS cases remains unknown, and no specific treatments have been established. The purpose of this study is to determine whether potassium supplements and/or the medication acetazolamide affect the duration of muscle weakness and heart rhythm abnormalities in people with ATS.
Read the detailed description
ATS is an ion channel disorder that causes episodes of muscle weakness and potentially life-threatening heart arrhythmias. The majority of ATS cases are caused by a mutation in the KCNJ2 gene, which is linked to potassium channels in the heart, brain, and skeletal muscle; other cases are presumed to be caused by an as yet undetermined gene lesion. To date, the treatment for ATS has been largely anecdotal, and no treatments have been formally assessed in a controlled clinical trial. This study will determine whether potassium supplements and/or acetazolamide, which is a diuretic medication, affect the duration of muscle weakness and heart rhythm abnormalities in people with ATS.
Participation in this study will last about 11 months. Participants will first attend a 3-day inpatient visit that will include a medical history, physical examination, blood work, heart rhythm testing by an electrocardiogram (ECG) and Holter monitor, strength testing, a health questionnaire, and daily potassium supplementation. Participants will also track the number and length of weakness episodes that they experience while in the hospital. On the last day of the inpatient visit, participants will be provided with multiple bottles containing either potassium or placebo. Participants will then return home for an 18-week treatment period that will consist of six 3-week-long treatments of either potassium or placebo, with the treatment schedule being randomly determined. Upon completing the first 18-week treatment period, participants will attend a second 3-day inpatient visit that will include the same tests and procedures as the first. The only difference will be that participants will receive acetazolamide along with potassium. This will be followed by a second 18-week treatment period that will consist of six 3-week-long treatments of either acetazolamide or placebo. At the end of the second treatment period, participants will fill out another health questionnaire. Throughout both 18-week treatment periods, participants will phone in daily to track any muscle or heart problems. They will also provide blood samples on a weekly basis. At Weeks 2, 5, 8, 11, 14, and 17 of both treatment periods, participants will wear a Holter monitor for 24 hours and then mail it in. A final outpatient visit will occur 8 weeks after the end of the second treatment period and will include heart rhythm testing, muscle strength testing, and blood work.
- Conditions
- Andersen-Tawil Syndrome
- Being tested
- Potassium, Acetazolamide
- Medical subject headings
- Andersen Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PotassiumDietary supplement
40 mEq twice daily in pill form during the first 3-day inpatient visit, followed by 40 mEq twice daily in liquid form during the first 18-week treatment period, as is randomly scheduled, and continued during the second 18-week treatment period as long as there are no limiting side effects
AcetazolamideDrug
250 mg twice daily, orally, during the second 3-day inpatient visit and during the second 18-week treatment period, as is randomly scheduled
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Participants will receive either potassium or placebo during six 3-week-long treatments, as randomly determined. Participants will then continue to receive potassium, if tolerated, and also either acetazolamide or placebo during another six 3-week-long treatments, as randomly determined. Receives: Dietary Supplement: Potassium; Drug: Acetazolamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Sum of the attack durations across the entire treatment period, reported by the participants via interactive voice response (IVR)
Measured: Measured over two 18-week treatments periods
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2009 (estimated)
- Study startDec 2008
- Primary completionJan 2011
- Study completionJan 2011
Why it stopped: Unable to recruit sufficient number of participants
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Andersen-Tawil SyndromeStudies of the same condition, open and under way.
- More trials run by University of RochesterThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Rochester
- Sponsor type
- University, hospital or other
- Collaborators
- Office of Rare Diseases (ORD), Rare Diseases Clinical Research Network, National Institute of Neurological Disorders and Stroke (NINDS)
- Responsible party
- Principal investigator, Robert Griggs, MD, University of Rochester
- Investigators
- Paul Twydell, DO, Principal investigator, University of Rochester School of Medicine & Dentistry
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00839501
- Sponsor's protocol ID
- RDCRN 5305
- Other IDs
- U54NS059065
- Status last verified
- Jan 2012
- First submitted
- 5 Feb 2009
- Last updated
- 20 Jan 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Jan 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Therapeutic Trial of Potassium and Acetazolamide in Andersen-Tawil Syndrome
- ClinicalTrials.gov ID
- NCT00839501
- Acronym / sponsor ID
- RDCRN 5305
- Conditions
- Andersen-Tawil Syndrome
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Unable to recruit sufficient number of participants
- Enrolment
- 3 participants (actual)
- Lead sponsor
- University of RochesterUniversity, hospital or other
- Collaborators
- Office of Rare Diseases (ORD), Rare Diseases Clinical Research Network, National Institute of Neurological Disorders and Stroke (NINDS)
- Study start
- Dec 2008
- Primary completion
- Jan 2011 (actual)
- Study completion
- Jan 2011 (actual)
- First posted
- 9 Feb 2009 (estimated)
- 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.
Andersen-Tawil Syndrome (ATS) is a rare genetic disorder that causes episodes of muscle weakness, potentially life-threatening changes in heart rhythm, and skeletal developmental abnormalities. The cause of some ATS cases remains unknown, and no specific treatments have been established. The purpose of this study is to determine whether potassium supplements and/or the medication acetazolamide affect the duration of muscle weakness and heart rhythm abnormalities in people with ATS.
Detailed description
ATS is an ion channel disorder that causes episodes of muscle weakness and potentially life-threatening heart arrhythmias. The majority of ATS cases are caused by a mutation in the KCNJ2 gene, which is linked to potassium channels in the heart, brain, and skeletal muscle; other cases are presumed to be caused by an as yet undetermined gene lesion. To date, the treatment for ATS has been largely anecdotal, and no treatments have been formally assessed in a controlled clinical trial. This study will determine whether potassium supplements and/or acetazolamide, which is a diuretic medication, affect the duration of muscle weakness and heart rhythm abnormalities in people with ATS.
Participation in this study will last about 11 months. Participants will first attend a 3-day inpatient visit that will include a medical history, physical examination, blood work, heart rhythm testing by an electrocardiogram (ECG) and Holter monitor, strength testing, a health questionnaire, and daily potassium supplementation. Participants will also track the number and length of weakness episodes that they experience while in the hospital. On the last day of the inpatient visit, participants will be provided with multiple bottles containing either potassium or placebo. Participants will then return home for an 18-week treatment period that will consist of six 3-week-long treatments of either potassium or placebo, with the treatment schedule being randomly determined. Upon completing the first 18-week treatment period, participants will attend a second 3-day inpatient visit that will include the same tests and procedures as the first. The only difference will be that participants will receive acetazolamide along with potassium. This will be followed by a second 18-week treatment period that will consist of six 3-week-long treatments of either acetazolamide or placebo. At the end of the second treatment period, participants will fill out another health questionnaire. Throughout both 18-week treatment periods, participants will phone in daily to track any muscle or heart problems. They will also provide blood samples on a weekly basis. At Weeks 2, 5, 8, 11, 14, and 17 of both treatment periods, participants will wear a Holter monitor for 24 hours and then mail it in. A final outpatient visit will occur 8 weeks after the end of the second treatment period and will include heart rhythm testing, muscle strength testing, and blood work.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Dietary Supplement: Potassium, Drug: AcetazolamideParticipants will receive either potassium or placebo during six 3-week-long treatments, as randomly determined. Participants will then continue to receive potassium, if tolerated, and also either acetazolamide or placebo during another six 3-week-long treatments, as randomly determined. |
Who may qualify
- Ages
- 10 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (21 listed)
- Clinically confirmed diagnosis of Andersen-Tawil Syndrome, as defined by at least two of the following three features:
- -OR-
- One of the three above criteria, with at leat one other family member meeting two criteria
- -OR-
- Not meeting clinical criteria but possessing the KCNJ2 mutation
Key exclusion criteria (7 listed)
- Sulfa allergy
- Renal impairment, as defined by serum creatine greater than 1.5 mg/dl
- History of renal calculi
- Cardiac disease or other disease that would make potassium supplementation or acetazolamide treatment inadvisable
- Diabetes mellitus
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 |
|---|---|---|
| Potassium40 mEq twice daily in pill form during the first 3-day inpatient visit, followed by 40 mEq twice daily in liquid form during the first 18-week treatment period, as is randomly scheduled, and continued during the second 18-week treatment period as long as there are no limiting side effects | Dietary supplement | 1 |
| Acetazolamide250 mg twice daily, orally, during the second 3-day inpatient visit and during the second 18-week treatment period, as is randomly scheduled | Drug | 1 |
Primary outcome
Sum of the attack durations across the entire treatment period, reported by the participants via interactive voice response (IVR)
Time frame: Measured over two 18-week treatments periods
Results and safety
The study was stopped early (reason given: Unable to recruit sufficient number of participants). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jan 2012.
Related trials for Andersen-Tawil Syndrome
Not yet recruitingPhase 2
N-of-1 in ATS and MEPPC
Andersen Tawil Syndrome, Multifocal Ectopic Purkinje-related Premature Contractions
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.
Paul Twydell, DO principal investigator
University of Rochester School of Medicine & Dentistry
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Potassium and Acetazolamide in people with Andersen-Tawil Syndrome, run by University of Rochester 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 21 inclusion and 7 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: stopped early, as of the sponsor's last update on 20 Jan 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. 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 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.
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 was stopped early (reason given: Unable to recruit sufficient number of participants). Results are not available in the source record.
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?
Sum of the attack durations across the entire treatment period, reported by the participants via interactive voice response (IVR) (time frame: Measured over two 18-week treatments periods). 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 20 Jan 2012.