NCT05662228

Therapies for Down Syndrome Regression Disorder

Mechanistic Investigation of Therapies for Down Syndrome Regression Disorder

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 66 (estimated)
• Sponsor: University of Colorado, Denver · Academic / Other
• Sex: All
• Age: 8 Years – 30 Years
• Healthy volunteers: Not accepted

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.

Detailed description

Recent published case reports and clinical experience of the investigators indicate Down Syndrome Regression Disorder (DSRD) may be successfully treated with immune-modulating therapies, in addition to current pharmacologic options. This study is a multidimensional clinical trial designed to advance the understanding of the etiology of DSRD and to evaluate the safety and efficacy of three distinct therapeutic approaches to treating DSRD: (1) the benzodiazepine lorazepam (Ativan™) (2) intravenous immunoglobulin (IVIG, Gammagard™) or (3) the JAK inhibitor tofacitinib (Xeljanz™). Participants will be randomized into one of the three treatment arms above for the 12-week study period, with a subset of participants undergoing an initial 12-week observational period. Specific Aims: 1. To define the relative safety profile of lorazepam, IVIG, and tofacitinib in DSRD. 2. To compare the efficacy of lorazepam, IVIG, and tofacitinib in DSRD. 3. To investigate potential mechanisms underlying DSRD and its response to therapies.

Conditions

• Down Syndrome
• Regression

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2023-06-29
• Primary completion: 2026-12-01
• Completion: 2026-12-01
• First posted: 2022-12-22
• Last updated: 2026-02-27

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study