RECRUITING

Therapies for Down Syndrome Regression Disorder

Conditions

Down Syndrome Regression Catatonia Autoimmune disorder Sleep Loss of skills Autoimmune Encephalopathy

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

Individuals with Down syndrome (DS) have an increased risk of numerous co-occurring conditions, including the neuropsychiatric condition known as Down Syndrome Regression Disorder (DSRD). A DSRD diagnosis often includes a sub-acute onset of catatonia, mutism, depersonalization, loss of ability to perform activities of daily living, hallucinations, delusions, and aggression and is most commonly observed in adolescents and young adults. The study evaluates the safety and efficacy of three currently prescribed therapies: lorazepam, intravenous immunoglobulin (IVIG) and tofacitinib.

Official Title

Mechanistic Investigation of Therapies for Down Syndrome Regression Disorder

Quick Facts

Study Start:2023-06-29

Study Completion:2026-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT05662228

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:8 Years to 30 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:CHILD, ADULT

Inclusion Criteria	Exclusion Criteria
* Individuals with DS between the ages of 8 and 30 years, inclusive. DS is broadly defined to include complete trisomy 21, Robertsonian translocation trisomy 21, partial trisomy 21 (segmental duplication), and mosaic trisomy 21. * Diagnosis of possible or probable DSRD per 2022 consensus guidelines. * Must agree to random treatment assignment. * Must agree to complete a washout of any medications intended to treat symptoms of DSRD or that may interfere with study interventions. * Must be able to present with a study partner or legal guardian at all study visits.	* Weight less than 40 kg. * Pregnant or breast feeding. * Past or current tobacco smoking. * Poor venous access not allowing repeated blood tests or non-compliance with venipuncture requirements. * Known allergies, hypersensitivity, or intolerance to lorazepam, IVIG, or tofacitinib. * Participants may be excluded for other unforeseen reasons or confounding reasons for DSRD symptoms at the study doctor's discretion. * Any co-occurring genetic disorder. * Active symptomatic cardiac disease. * Clinically significant chronic or active viral infection, including but not limited to HIV, hepatitis, CMV, EBV, HSV or untreated tuberculosis. * Untreated chronic or active bacterial infection. * Untreated hypothyroidism or hyperthyroidism. * History of disseminated herpes zoster, disseminated herpes simplex, or recurrent localized dermatomal herpes zoster. * History of malignancy (solid tumor or leukemia). * Moyamoya syndrome or stroke (active or prior). * Baseline abnormal renal function indicative of moderate or severe renal disease by eGFR \<=45. * History of acute narrow-angle glaucoma. * History of venous or arterial thrombosis. * IgA deficiency with antibodies against IgA. * Pathogenic neuronal autoantibody positivity against established causes of autoimmune encephalopathy in CSF. * Any subject with a history of anaphylaxis or a severe systemic response to blood or plasma-derived products. * Any vaccination planned during the study or within the last 6 weeks. * Use of electroconvulsive therapy, lorazepam, or a JAK inhibitor within the last 4 weeks. * Use of IVIG within the last 8 weeks. * Use of immunosuppressant drugs (e.g., prednisone, mycophenolate mofetil, azathioprine) within the last 8 weeks. * Use of rituximab within the past 6 months, unless B cell levels have recovered and are above 50 cells/uL. * Use of other immunosuppressant biologics (e.g., adalimumab, etanercept) within the past 6 months. * Use of strong CP3A4 inhibitors or inducers (e.g., ketoconazole, rifampin) within the last 4 weeks. * Use of moderate CP3A4 inhibitors with a strong CYP2C19 inhibitor (e.g., fluconazole) within the last 4 weeks. * Use of moderate CYP2C9 inhibitors (e.g., valproic acid) within the last 4 weeks. * Use of strong CYP1A2 inducers (e.g., phenobarbital) or moderate CYP1A2 inhibitors (e.g., fluvoxamine) within the last 4 weeks. * Use of certain mood stabilizers or anticonvulsants (e.g., clonazepam, lithium, oxcarbazepine) within the last 4 weeks. * Any prior use of methotrexate, cyclophosphamide, or other chemotherapeutics. * Any prior solid organ transplant. * Any prior neurosurgical intervention. * Any subject who has received blood or plasma products ≤ 30 days prior to first Baseline visit.

Inclusion Criteria

Exclusion Criteria

* Individuals with DS between the ages of 8 and 30 years, inclusive. DS is broadly defined to include complete trisomy 21, Robertsonian translocation trisomy 21, partial trisomy 21 (segmental duplication), and mosaic trisomy 21.
* Diagnosis of possible or probable DSRD per 2022 consensus guidelines.
* Must agree to random treatment assignment.
* Must agree to complete a washout of any medications intended to treat symptoms of DSRD or that may interfere with study interventions.
* Must be able to present with a study partner or legal guardian at all study visits.

* Weight less than 40 kg.
* Pregnant or breast feeding.
* Past or current tobacco smoking.
* Poor venous access not allowing repeated blood tests or non-compliance with venipuncture requirements.
* Known allergies, hypersensitivity, or intolerance to lorazepam, IVIG, or tofacitinib.
* Participants may be excluded for other unforeseen reasons or confounding reasons for DSRD symptoms at the study doctor's discretion.
* Any co-occurring genetic disorder.
* Active symptomatic cardiac disease.
* Clinically significant chronic or active viral infection, including but not limited to HIV, hepatitis, CMV, EBV, HSV or untreated tuberculosis.
* Untreated chronic or active bacterial infection.
* Untreated hypothyroidism or hyperthyroidism.
* History of disseminated herpes zoster, disseminated herpes simplex, or recurrent localized dermatomal herpes zoster.
* History of malignancy (solid tumor or leukemia).
* Moyamoya syndrome or stroke (active or prior).
* Baseline abnormal renal function indicative of moderate or severe renal disease by eGFR \<=45.
* History of acute narrow-angle glaucoma.
* History of venous or arterial thrombosis.
* IgA deficiency with antibodies against IgA.
* Pathogenic neuronal autoantibody positivity against established causes of autoimmune encephalopathy in CSF.
* Any subject with a history of anaphylaxis or a severe systemic response to blood or plasma-derived products.
* Any vaccination planned during the study or within the last 6 weeks.
* Use of electroconvulsive therapy, lorazepam, or a JAK inhibitor within the last 4 weeks.
* Use of IVIG within the last 8 weeks.
* Use of immunosuppressant drugs (e.g., prednisone, mycophenolate mofetil, azathioprine) within the last 8 weeks.
* Use of rituximab within the past 6 months, unless B cell levels have recovered and are above 50 cells/uL.
* Use of other immunosuppressant biologics (e.g., adalimumab, etanercept) within the past 6 months.
* Use of strong CP3A4 inhibitors or inducers (e.g., ketoconazole, rifampin) within the last 4 weeks.
* Use of moderate CP3A4 inhibitors with a strong CYP2C19 inhibitor (e.g., fluconazole) within the last 4 weeks.
* Use of moderate CYP2C9 inhibitors (e.g., valproic acid) within the last 4 weeks.
* Use of strong CYP1A2 inducers (e.g., phenobarbital) or moderate CYP1A2 inhibitors (e.g., fluvoxamine) within the last 4 weeks.
* Use of certain mood stabilizers or anticonvulsants (e.g., clonazepam, lithium, oxcarbazepine) within the last 4 weeks.
* Any prior use of methotrexate, cyclophosphamide, or other chemotherapeutics.
* Any prior solid organ transplant.
* Any prior neurosurgical intervention.
* Any subject who has received blood or plasma products ≤ 30 days prior to first Baseline visit.

Contacts and Locations

Study Contact

Angela Rachubinski, PhD

CONTACT

303-724-7366

DSresearch@cuanschutz.edu

Belinda Enriquez Estrada, MS

CONTACT

303-724-0491

DSresearch@cuanschutz.edu

Principal Investigator

Joaquin Espinosa, PhD

PRINCIPAL_INVESTIGATOR

Linda Crnic Institute for Down Syndrome

Elise Sannar, MD

PRINCIPAL_INVESTIGATOR

Children's Hospital Colorado

Jonathon Santoro, MD

PRINCIPAL_INVESTIGATOR

Children's Hospital Los Angeles

Study Locations (Sites)

Children's Hospital Los Angeles

Los Angeles, California, 90027

United States

Children's Hospital Colorado

Aurora, Colorado, 80045

United States

Collaborators and Investigators

Sponsor: University of Colorado, Denver

Joaquin Espinosa, PhD, PRINCIPAL_INVESTIGATOR, Linda Crnic Institute for Down Syndrome
Elise Sannar, MD, PRINCIPAL_INVESTIGATOR, Children's Hospital Colorado
Jonathon Santoro, MD, PRINCIPAL_INVESTIGATOR, Children's Hospital Los Angeles

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-06-29

Study Completion Date2026-12

Study Record Updates

Study Start Date2023-06-29

Study Completion Date2026-12

Terms related to this study

Keywords Provided by Researchers

Catatonia
Autoimmune disorder
Sleep
Loss of skills
Autoimmune Encephalopathy

Additional Relevant MeSH Terms

Down Syndrome
Regression