ROHHAD SyndromeNCT02441491
Treatment of Rapid Onset Obesity, Hypoventilation, Hypothalamic Dysfunction, and Autonomic Dysregulation (ROHHAD )
A study testing Cyclophosphamide in people with ROHHAD Syndrome, run by Johns Hopkins University at 1 site in United States.
Trial summary
ROHHAD (rapid onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation) syndrome is a rare pediatric disorder associated with a cancer called neuroblastoma and presumed to be driven by an attack of the immune system on specific area in the brain. Read more about this study
- Who is it for?
- Ages 12 months to 22 years
- Conditions the study is for
- ROHHAD Syndrome
- What is being tested?
- Cyclophosphamide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2015to 31 Mar 2024
- Phase
- Interventional
- 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 12 months to 22 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis of ROHHAD syndrome confirmed by two physicians.
- Any symptomatic improvement in response to a course of rituximab (five weekly doses) as assessed by parents and/or treating physician
- Normal brain MRI
- Cared for at home by the family
- Patients requiring bilevel positive airway pressure (BiPAP) support are eligible
- Negative pregnancy test for post pubertal female patients
Who cannot join
- Cardiac ejection fraction <40% or shortening fraction <20%.
- Inadequate pulmonary function, i.e. forced vital capacity or forced expiratory volume at one second < 50% of predicted for children greater than 8 years of age, or oxygen saturation <93% on pulse oximetry for younger children.
- Ventilator dependent
- Known chromosomal abnormality
- Active cancer diagnosis. Neuroblastoma that requires only follow up is eligible.
- Pregnancy
Trial locations and contacts
1 site in 1 country.
United States1 site
Sidney Kimmel Cancer Center
Baltimore, Maryland, 21287
About this study
Official title: High-dose Cyclophosphamide for the Treatment of ROHHAD (Rapid Onset Obesity, Hypoventilation, Hypothalamic Dysfunction, and Autonomic Dysregulation) Syndrome
ROHHAD (rapid onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation) syndrome is a rare pediatric disorder associated with a cancer called neuroblastoma and presumed to be driven by an attack of the immune system on specific area in the brain. Patients develop severe symptoms and often succumb to this disease. Based on the researchers' experience the investigators conduct a clinical trial to study intensive immunosuppression with high-dose cyclophosphamide in these patients. In addition to describing the symptomatic improvement, the investigators' trial seeks to define objective markers of disease activity.
Read the detailed description
Baseline evaluation will include:
Sleep study and pulmonary evaluation Hormone levels Determination of up to 6 key ROHHAD-related symptoms to be followed Hyperphagia questionnaire 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (FDG) positron emission tomography (PET) scan Dual energy x-ray absorptiometry (DXA) scan Cerebrospinal fluid (CSF) analysis
Patients will be treated with cyclophosphamide, 50 mg/kg (ideal body weight)/dose daily for 4 days, with Mesna and hydration as prophylaxis against hemorrhagic cystitis. Supportive care will include mucosal care, transfusions, infection prophylaxis, and empiric treatment for febrile neutropenia.
Composite severity score will be assessed to measure response of key symptoms, and formal neuropsychological testing, sleep study, and hormone studies will be performed.
- Conditions
- ROHHAD Syndrome
- Being tested
- Cyclophosphamide
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Also called Cytoxan
Cyclophosphamide will be given by vein once a day for four straight days.
Ten days after starting cyclophosphamide, filgrastim, a drug that helps normal blood cells to grow, by vein once every day to try to help your blood cells grow faster.
| Study group | Role | What they receive |
|---|---|---|
| Cyclophosphamide | Experimental | Cyclophosphamide will be given by vein once a day for four straight days.
Ten days after starting cyclophosphamide, filgrastim, a drug that helps normal blood cells to grow, will be given by vein once every day to try to help your blood cells grow faster. Receives: Drug: Cyclophosphamide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Symptomatic improvement on the ROHHAD Symptoms Scale of children with ROHHAD syndrome after treatment with high-dose cyclophosphamide .
Measured: 18 months
Safety and toxicity of high-dose cyclophosphamide used to treat children with ROHHAD of as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Measured: 18 months
Secondary outcomes (2)
To calculate Area Under Curve (AUC) of high dose cyclophosphamide in obese children.
Measured: predose, 0, 1, 2, 4, 8, 12 and 24 hrs from the completion of infusion.
Neuropsychological function of patients with ROHHAD before and after high-dose cyclophosphamide measured using complementary age appropriate evaluation tools including Wechsler Preschool and Primary Scale of Intelligence RAN objects, and AIM.
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 May 2015 (estimated)
- Study startMar 2015
- Primary completion31 Mar 2024
- Study completion31 Mar 2024
Why it stopped: Inadequate accrual
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 ROHHAD SyndromeStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe 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 N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Allen Chen, MD, PhD, Study chair, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02441491
- Sponsor's protocol ID
- IRB00060912
- Other IDs
- J1520
- Status last verified
- Apr 2024
- First submitted
- 8 Apr 2015
- Last updated
- 2 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Jacobson LA, Rane S, McReynolds LJ, Steppan DA, Chen AR, Paz-Priel I. Improved Behavior and Neuropsychological Function in Children With ROHHAD After High-Dose Cyclophosphamide. Pediatrics. 2016 Jul;138(1):e20151080. doi: 10.1542/peds.2015-1080. Epub 2016 Jun 16.
PubMed 27313069
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- High-dose Cyclophosphamide for the Treatment of ROHHAD (Rapid Onset Obesity, Hypoventilation, Hypothalamic Dysfunction, and Autonomic Dysregulation) Syndrome
- ClinicalTrials.gov ID
- NCT02441491
- Acronym / sponsor ID
- IRB00060912
- Conditions
- ROHHAD Syndrome
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Inadequate accrual
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Study start
- Mar 2015
- Primary completion
- 31 Mar 2024 (actual)
- Study completion
- 31 Mar 2024 (actual)
- First posted
- 12 May 2015 (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.
ROHHAD (rapid onset obesity, hypothalamic dysfunction, hypoventilation, and autonomic dysregulation) syndrome is a rare pediatric disorder associated with a cancer called neuroblastoma and presumed to be driven by an attack of the immune system on specific area in the brain. Patients develop severe symptoms and often succumb to this disease. Based on the researchers' experience the investigators conduct a clinical trial to study intensive immunosuppression with high-dose cyclophosphamide in these patients. In addition to describing the symptomatic improvement, the investigators' trial seeks to define objective markers of disease activity.
Detailed description
Baseline evaluation will include:
Sleep study and pulmonary evaluation Hormone levels Determination of up to 6 key ROHHAD-related symptoms to be followed Hyperphagia questionnaire 18F-2-fluoro-2-deoxy-D-glucose fluorodeoxyglucose (FDG) positron emission tomography (PET) scan Dual energy x-ray absorptiometry (DXA) scan Cerebrospinal fluid (CSF) analysis
Patients will be treated with cyclophosphamide, 50 mg/kg (ideal body weight)/dose daily for 4 days, with Mesna and hydration as prophylaxis against hemorrhagic cystitis. Supportive care will include mucosal care, transfusions, infection prophylaxis, and empiric treatment for febrile neutropenia.
Composite severity score will be assessed to measure response of key symptoms, and formal neuropsychological testing, sleep study, and hormone studies will be performed.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Cyclophosphamide | Experimental | Drug: CyclophosphamideCyclophosphamide will be given by vein once a day for four straight days. Ten days after starting cyclophosphamide, filgrastim, a drug that helps normal blood cells to grow, will be given by vein once every day to try to help your blood cells grow faster. |
Who may qualify
- Ages
- 12 months to 22 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (6 listed)
- Diagnosis of ROHHAD syndrome confirmed by two physicians.
- Any symptomatic improvement in response to a course of rituximab (five weekly doses) as assessed by parents and/or treating physician
- Normal brain MRI
- Cared for at home by the family
- Patients requiring bilevel positive airway pressure (BiPAP) support are eligible
Key exclusion criteria (6 listed)
- Cardiac ejection fraction <40% or shortening fraction <20%.
- Inadequate pulmonary function, i.e. forced vital capacity or forced expiratory volume at one second < 50% of predicted for children greater than 8 years of age, or oxygen saturation <93% on pulse oximetry for younger children.
- Ventilator dependent
- Known chromosomal abnormality
- Active cancer diagnosis. Neuroblastoma that requires only follow up is eligible.
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 |
|---|---|---|
| CyclophosphamideAlso: CytoxanCyclophosphamide will be given by vein once a day for four straight days. Ten days after starting cyclophosphamide, filgrastim, a drug that helps normal blood cells to grow, by vein once every day to try to help your blood cells grow faster. | Drug | Cyclophosphamide |
Primary outcome
Symptomatic improvement on the ROHHAD Symptoms Scale of children with ROHHAD syndrome after treatment with high-dose cyclophosphamide .
Time frame: 18 months
Safety and toxicity of high-dose cyclophosphamide used to treat children with ROHHAD of as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) v4.0.
Time frame: 18 months
2 secondary outcomes
To calculate Area Under Curve (AUC) of high dose cyclophosphamide in obese children.
Time frame: predose, 0, 1, 2, 4, 8, 12 and 24 hrs from the completion of infusion.
Neuropsychological function of patients with ROHHAD before and after high-dose cyclophosphamide measured using complementary age appropriate evaluation tools including Wechsler Preschool and Primary Scale of Intelligence RAN objects, and AIM.
Time frame: 18 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2024.
- Derived from this study: PubMed 27313069Jacobson LA, Rane S, McReynolds LJ, Steppan DA, Chen AR, Paz-Priel I. Improved Behavior and Neuropsychological Function in Children With ROHHAD After High-Dose Cyclophosphamide. Pediatrics. 2016 Jul;138(1):e20151080. doi: 10.1542/peds.2015-1080. Epub 2016 Jun 16.
Related trials for ROHHAD Syndrome
RecruitingObservational study
International Rapid-onset Obesity With Hypothalamic Dysfunction, Hypoventilation & Autonomic Dysregulation (ROHHAD) Registry
ROHHAD, Rapid-Onset Obesity With Hypothalamic Dysfunction, Hypoventilation & Autonomic Dysregulation
RecruitingObservational study
Whole Transcriptome Profiling and Metabolic Phenotyping in Children With ROHHAD Syndrome
Childhood Obesity, Morbid Obesity
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.
Allen Chen, MD, PhD study chair
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cyclophosphamide in people with ROHHAD Syndrome, run by Johns Hopkins University 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 6 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: withdrawn, as of the sponsor's last update on 2 Apr 2024. 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.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Symptomatic improvement on the ROHHAD Symptoms Scale of children with ROHHAD syndrome after treatment with high-dose cyclophosphamide . (time frame: 18 months). The study lists 2 primary outcomes in all. 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 NCT02441491, 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 2 Apr 2024.