Therapies for Down Syndrome Regression Disorder

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

Interventions

DRUG

Lorazepam

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.

DRUG

Intravenous immunoglobulin (IVIG)

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.

DRUG

Tofacitinib

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

Sponsors & Collaborators

• Children's Hospital Los Angeles

  collaborator OTHER

• University of Colorado, Denver

  lead OTHER

Principal Investigators

• Joaquin Espinosa, PhD · Linda Crnic Institute for Down Syndrome

• Elise Sannar, MD · Children's Hospital Colorado

• Jonathon Santoro, MD · Children's Hospital Los Angeles

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

8 Years

Max Age

30 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-06-29

Primary Completion

2026-12-31

Completion

2026-12-31

FDA Drug

Yes

Countries

• United States

Study Locations