Treatments for Down Syndrome Regression Disorder

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This clinical trial evaluates the safety and efficacy of three therapies for Down Syndrome Regression Disorder (DSRD), a neuropsychiatric condition affecting individuals with Down syndrome. Participants aged 8 to 30 will be randomized to receive either lorazepam, intravenous immunoglobulin (IVIG), or tofacitinib over a 12-week period. The study aims to define the safety profiles of these treatments, compare their effectiveness, and explore the underlying mechanisms of DSRD. A subset of participants will also undergo an initial observational period to gather additional data.

Why it matters

Who can join: the full rules

Inclusion 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.

Exclusion Criteria:

General

* 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.

Co-occurring Conditions

* 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.

Medications or Interventions

* 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.

Where it's running

• Children's Hospital Los Angeles
  Los Angeles, California, United States Recruiting
• Children's Hospital Colorado
  Aurora, Colorado, United States Recruiting

Study contacts

• Principal investigator: Joaquin Espinosa, PhD — Linda Crnic Institute for Down Syndrome
• Study coordinator: Angela Rachubinski, PhD
• Email: DSresearch@cuanschutz.edu
• Phone: 303-724-7366

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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• JAK inhibitor treatment for Down syndrome in children and young adults

  This study tests whether 6 months of tofacitinib can help improve safety and neurodevelopment in people with Down syndrome aged 6 to 22, compared with placebo.

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• Jump rope to improve navicular drop and foot posture in children with Down syndrome

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• Thymus removal and immune aging in people with Down syndrome

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.