Therapies for Down Syndrome Regression Disorder

NCT05662228 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 22-1992
• Study Type: interventional
• Target: 66
• Locations: 1 country
• Sites: 2

Brief Summary

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.

Conditions

Down Syndrome; Regression

Keywords

Catatonia; Autoimmune disorder; Sleep; Loss of skills; Autoimmune Encephalopathy

Outcome Measures

Primary Outcomes (1)

• Comparison of number and severity of all adverse events.

  A summary of adverse events (AEs) by type and organ system will be reported for the entire study period, along with any statistically significant differences observed in rates of AEs across treatment arms.

  Baseline to 14 weeks

Secondary Outcomes (7)

• Change in catatonia by overall score in BFCRS.

  Baseline to 12 weeks

• Time to complete 25-Foot Walk assessment.

  Baseline to 12 weeks

• Total number of errors in visual motor assessment NEPSY-II.

  Baseline to 12 weeks

• Change in expressive language as measured by total number of words used.

  Baseline to 12 weeks

• Change in adaptive skills as measured by the VABS-3 domain level standard score.

  Baseline to 12 weeks

Other Outcomes (4)

• Change in social interaction as measured by SRS-2 subdomain T-scores.

  Baseline to 12 weeks

• Change in behavior as measured by DBC-2 T-score.

  Baseline to 12 weeks

• Change in one or more measures of overall cognitive ability.

  Baseline to 12 weeks

Study Arms (3)

Lorazepam

EXPERIMENTAL

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).

Drug: Lorazepam

Intravenous immunoglobulin (IVIG)

EXPERIMENTAL

Participants will receive 4 doses of IVIG treatment over 12 weeks.

Drug: Intravenous immunoglobulin (IVIG)

Tofacitinib

EXPERIMENTAL

Tofacitinib will be administered as an oral pill at 5 mg twice daily over the 12-week study.

Drug: Tofacitinib

Interventions

Lorazepam DRUG

Lorazepam will be administered as an oral pill over the first 15 days of study in a daily titration, starting at 0.5 mg BID and increasing to up to 2 mg three times daily, as tolerated. Dosing will continue at the maximum tolerated dose through the 12-week endpoint. Participants will be titrated off lorazepam over at least four weeks after completing the endpoint visit. Taper will be tailored to individuals for safety reasons with a goal of decreasing dosage by 25% weekly. Phone check ins will be conducted every three days to monitor patient.

Also known as: Ativan

Lorazepam

Intravenous immunoglobulin (IVIG) DRUG

IVIG will be administered as a series of four intravenous infusions at a dose of 1 mg/kg with pre-infusion medications of 1 mg/kg diphenhydramine and 15 mg/kg acetaminophen. The first two infusions occur at baseline and one day after (induction dosing), followed by one infusion at 4 weeks and one infusion at 8 weeks.

Also known as: Gammagard Liquid (immune globulin infusion [human] 10%)

Intravenous immunoglobulin (IVIG)

Tofacitinib DRUG

Tofacitinib will be administered as an oral pill at 5 mg twice daily over the 12-week study.

Also known as: Xeljanz

Tofacitinib

Eligibility Criteria

• Age: 8 Years - 30 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Colorado, Denver: lead
• Children's Hospital Los Angeles: collaborator

Study Sites (2)

Children's Hospital Los Angeles

Los Angeles, California, 90027, United States

Location

Children's Hospital Colorado

Aurora, Colorado, 80045, United States

Location

MeSH Terms

Conditions

Down Syndrome; Catatonia; Autoimmune Diseases; Autoimmune Diseases of the Nervous System

Interventions

Lorazepam; Immunoglobulins, Intravenous; tofacitinib

Condition Hierarchy (Ancestors)

Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Chromosome Disorders; Genetic Diseases, Inborn; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior; Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzodiazepinones; Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Immunoglobulin G; Immunoglobulin Isotypes; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Joaquin Espinosa, PhD

  Linda Crnic Institute for Down Syndrome

  PRINCIPAL INVESTIGATOR

• Elise Sannar, MD

  Children's Hospital Colorado

  PRINCIPAL INVESTIGATOR

• Jonathon Santoro, MD

  Children's Hospital Los Angeles

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: We will use covariate-adaptive randomization to assign participants to one of three treatment arms while accounting for sex, age, and other medical history.

Study Record Dates

• First Submitted: December 8, 2022
• First Posted: December 22, 2022
• Study Start: June 29, 2023
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: February 27, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Data will be made available upon publication in a peer-reviewed journal.
• Access Criteria: Data access requests will be reviewed by the sponsor-investigator and collaborators.

Locations

US (2)