Multiple Therapies for Down Syndrome Regression Disorder
Recruiting in Palo Alto (17 mi)
+1 other location
Age: < 65
Sex: Any
Travel: May be covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: University of Colorado, Denver
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?This trial is testing three treatments for Down Syndrome Regression Disorder (DSRD) in people with Down Syndrome. The treatments include a calming medication, an immune-boosting blood product, and a drug that reduces immune activity. The goal is to see which treatment is safest and most effective for managing severe symptoms.
Will I have to stop taking my current medications?
Yes, you will need to stop taking any medications that are meant to treat symptoms of Down Syndrome Regression Disorder or that might interfere with the study treatments. There is a 'washout period' required for certain medications, meaning you must stop taking them for a specific time before starting the trial.
What data supports the effectiveness of the drug Intravenous Immunoglobulin (IVIG) for treating Down Syndrome Regression Disorder?
Research shows that Intravenous Immunoglobulin (IVIG) has been effective in treating conditions like primary immunodeficiency and Landau-Kleffner syndrome, where it improved symptoms such as speech and behavior. This suggests it might help with similar symptoms in Down Syndrome Regression Disorder.
12345Is lorazepam generally safe for use in humans?
Lorazepam is generally considered safe for use in humans, but it can sometimes cause unexpected reactions, such as worsening seizures in some cases.
678910How is the drug for Down Syndrome Regression Disorder different from other treatments?
This drug combination is unique because it includes intravenous immunoglobulin (IVIG), which is typically used for immune deficiencies and inflammatory conditions, along with lorazepam, a medication for anxiety, and tofacitinib, a drug that modulates the immune system. This combination targets both immune and behavioral aspects of the disorder, which is not common in standard treatments.
111121314Eligibility Criteria
This trial is for individuals aged 8-30 with Down Syndrome who may have Down Syndrome Regression Disorder (DSRD), which includes symptoms like catatonia and hallucinations. Participants must not be on certain medications, have specific health conditions like heart disease or severe infections, or a history of allergies to the study drugs.Inclusion Criteria
I agree to stop taking certain medications for my condition during the study.
Exclusion Criteria
My tests show I have antibodies in my brain that could cause inflammation.
I have had blood clots in my veins or arteries.
I have had cancer before.
I have not treated my underactive or overactive thyroid.
I have had Moyamoya syndrome or a stroke.
I do not have any significant ongoing or chronic viral infections like HIV or hepatitis.
I have an ongoing or untreated bacterial infection.
I have a history of acute narrow-angle glaucoma.
I haven't used immunosuppressant drugs like adalimumab in the last 6 months.
I haven't taken drugs like valproic acid in the last 4 weeks.
I have previously used methotrexate, cyclophosphamide, or other chemotherapy drugs.
I have had brain surgery before.
I have heart problems that show symptoms.
My kidney function is moderately or severely reduced.
I weigh less than 40 kg.
I have an IgA deficiency and antibodies against IgA.
I have a genetic disorder along with my current condition.
I haven't taken certain strong medications in the last 4 weeks.
I haven't taken immunosuppressant drugs in the last 8 weeks.
Participant Groups
The trial tests the safety and effectiveness of lorazepam, intravenous immunoglobulin (IVIG), and tofacitinib in treating DSRD. Patients will be randomly assigned one of these treatments and monitored for their response.
3Treatment groups
Experimental Treatment
Group I: TofacitinibExperimental Treatment1 Intervention
Tofacitinib will be administered as an oral pill at 5 mg twice daily over the 12-week study.
Group II: LorazepamExperimental Treatment1 Intervention
Participants will receive lorazepam as an oral pill three times daily for 12 weeks as well as titration doses for an additional 4 weeks (approximately).
Group III: Intravenous immunoglobulin (IVIG)Experimental Treatment1 Intervention
Participants will receive 4 doses of IVIG treatment over 12 weeks.
Intravenous immunoglobulin (IVIG) is already approved in United States, European Union, Canada for the following indications:
🇺🇸 Approved in United States as IVIG for:
- Primary immunodeficiency diseases
- Chronic inflammatory demyelinating polyneuropathy (CIDP)
- Multifocal motor neuropathy
- Kawasaki disease
- Immune thrombocytopenic purpura (ITP)
- Autoimmune hemolytic anemia
- Neonatal alloimmune thrombocytopenia
- Down Syndrome Regression Disorder (off-label)
🇪🇺 Approved in European Union as IVIG for:
- Primary immunodeficiency diseases
- Chronic inflammatory demyelinating polyneuropathy (CIDP)
- Multifocal motor neuropathy
- Kawasaki disease
- Immune thrombocytopenic purpura (ITP)
- Autoimmune hemolytic anemia
- Neonatal alloimmune thrombocytopenia
🇨🇦 Approved in Canada as IVIG for:
- Primary immunodeficiency diseases
- Chronic inflammatory demyelinating polyneuropathy (CIDP)
- Multifocal motor neuropathy
- Kawasaki disease
- Immune thrombocytopenic purpura (ITP)
- Autoimmune hemolytic anemia
- Neonatal alloimmune thrombocytopenia
Find A Clinic Near You
Research locations nearbySelect from list below to view details:
Children's Hospital Los AngelesLos Angeles, CA
Children's Hospital ColoradoAurora, CO
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Who is running the clinical trial?
University of Colorado, DenverLead Sponsor
Children's Hospital Los AngelesCollaborator
References
Efficacy and safety of human intravenous immunoglobulin 5% (Ig VENA) in pediatric patients affected by primary immunodeficiency. [2021]Patients affected by primary immunodeficiencies are characterized for high susceptibility for severe infections. Our data demonstrate Kedrion 5% intravenous immunoglobulin G (IVIg) treatment effective and safe as replacement therapy for children and adolescents affected by primary immunodeficiency. The particularities of our study are the selection of a long period of follow-up (71 patient-years of follow-up), and to the best of our knowledge, our study is one of few that assesses the safety and efficacy of intravenous immunoglobulin treatment of primary immunodeficiency specifically in a pediatric population.
Efficacy of intravenous immunoglobulin in Landau-Kleffner syndrome. [2019]We administered 2 gm/kg of intravenous gamma globulin (IVIG) to each of five consecutive patients with Landau-Kleffner syndrome, over 4 days. We compared the 1-month baseline to that following IVIG using a severity score assessing speech, comprehension, behavior, seizures, and electroencephalography. There was a significant drop in this score after IVIG (P = 0.025). Two patients had a dramatic response to IVIG, with complete resolution of symptoms. This finding suggests that IVIG has at least some efficacy for the therapy of Landau-Kleffner syndrome.
Outcomes of ICU patients treated with intravenous immunoglobulin for sepsis or autoimmune diseases. [2022]To evaluate the outcomes of hospitalized patients in two intensive care units (ICU) treated with intravenous immunoglobulin (IVIg) added to standard-of-care therapy. The indications for IVIg therapy were sepsis or autoimmune disease.
Benefits of immunoglobulin substitution in primary and secondary immunodeficiencies: Interim analysis of a prospective, long-term non-interventional study. [2021]To assess the safety, tolerability, and effectiveness of the intravenous immunoglobulin (IVIG) Intratect 100 g/L in a prospective, large-scale non-interventional study (NIS) of patients with a wide range of antibody deficiencies as well as other indications for IVIG, risk factors, and frequency of pre-treatments.
[Intravenous immunoglobulin in the treatment of malignant epilepsy in children]. [2006]15 children with malignant epilepsy showing no response to conventional antiepileptic drugs or hormone therapy were administered intravenous immunoglobulin (Endobulin, Immuno) at a dosage of 400 mg/kg per day on the 1st and 15th day and subsequently every three weeks for 6 months. 7 of these 15 patients showed IgG2 subclass deficiency. A significant reduction in attacks, or even absence of attacks was observed in 10 out of 15 children after six months of intravenous immunoglobulin therapy. Apart from one patient with ringchromosomopathy, all the children with IgG2 subclass deficiency responded to this therapy. The reduction of attacks after i.v. immunoglobulin therapy correlates with the improvement or normalization of the EEG findings. At present, the authors consider the number of patients still too small to make a final assessment, but they believe that intravenous immunoglobulin holds an important position in the treatment of malignant epilepsy in childhood.
Lorazepam v. diazepam for pediatric status epilepticus. [2017]Clinical question Is intravenous (IV) lorazepam superior to IV diazepam in the treatment of pediatric status epilepticus? Article chosen Chamberlain JM, Okada P, Holsti M, et al. Lorazepam v. diazepam for pediatric status epilepticus: a randomized clinical trial. JAMA 2014;311(16):1652-60.
A cost analysis of enterally administered lorazepam in the pediatric intensive care unit. [2019]To determine the cost savings of replacing intravenous midazolam with enterally administered lorazepam in mechanically ventilated children who require long-term continuous sedation.
Comparison of intranasal midazolam versus intravenous lorazepam for seizure termination and prevention of seizure clusters in the adult epilepsy monitoring unit. [2020]The objective of the study was to compare the performance of intravenous (IV) lorazepam (IVL) and intranasal midazolam (INM) for seizure termination and prevention of seizure clusters in adults admitted to the epilepsy monitoring unit (EMU) in whom seizures were captured on continuous video-electroencephalogram.
Paradoxical precipitation of tonic seizures by lorazepam in a child with atypical absence seizures. [2019]A 10-year-old girl with Lennox-Gastaut syndrome who received intravenous lorazepam for atypical absence status seizures is reported. Tonic seizures occurred immediately and appeared to represent a paradoxical seizure exacerbation. We also review other patients with paradoxical seizure exacerbation by benzodiazepines.
[Use of injectable lorazepam in status epilepticus: a comparative study in French-speaking hospitals]. [2015]Injectable lorazepam (IL) is marketed in many countries but in France is only available within the framework of a compassionate use program for refractory status epilepticus. This study aims to evaluate the differences of pediatric use and status of IL in the hospitals of the Mother-Child French-speaking Network (Réseau mère-enfant de la francophonie, i.e., RMEF).
Behavior abnormality following intravenous immunoglobulin treatment in patients with primary antibody deficiencies. [2010]Treatment with intravenous immunoglobulin (IVIG) is considered a safe therapy for patients with primary antibody deficiencies (PADs), whilst adverse effects have been frequently reported. Meantime behavioral disorders reactions have not been reported yet. In this study, we describe for the first time a group of patients with PADs, who were under IVIG therapy and experienced some behavioral disorders.
Clinical Outcomes of Low-Dose Methotrexate Therapy as a Second-Line Drug for Intravenous Immunoglobulin-Resistant Kawasaki Disease. [2018]Intravenous immunoglobulin (IVIG) is the standard treatment for Kawasaki disease (KD). However, there is still no standard treatment for IVIG-resistant KD. This study aimed to evaluate the efficacy of low-dose methotrexate (MTX) as a treatment for IVIG-resistant KD.
Changing trends in IVIG use in pediatric patients: A retrospective review of practices in a network of major USA pediatric hospitals. [2020]The use of immunoglobulins is gradually increasing. Intravenous immunoglobulins (IVIG) are used as replacement therapy for primary and secondary immune deficiencies, and as an anti-inflammatory and immunomodulatory medication for the treatment of neurologic, dermatologic, and rheumatologic diseases. The objective of this study was to analyze trends in the IVIG use in pediatric patients hospitalized to 47 US-based children's hospitals from 2007 to 2014. IVIG was used for the treatment of >2300 primary diagnoses in 53,648 unique patients. The number of IVIG admissions increased by 30.2% during the study period, while the mean rate of IVIG admissions/100,000 admissions increased only 5.8%. Most patients receiving IVIG were children and adolescents. IVIG was frequently used off-label or for the treatment of FDA-approved indications in children under two years of age and BMT patients
Real-world experience with CLAIRYG® 50 mg/mL (intravenous immunoglobulin) in children under 12 years with primary immunodeficiency or immmune thrombocytopenia: a post-approval safety study. [2023]Label="Introduction" NlmCategory="UNASSIGNED">This study presents the results of a real-life, multicenter, prospective, post-approval safety evaluation of Clairyg® 50 mg/mL, a 5% intravenous immunoglobulin (IVIg) liquid, in 59 children (aged < 12 years) with primary immunodeficiency diseases (PID) (n = 32) or immune thrombocytopenia (ITP) (n = 27) in France.