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Down SyndromePhase 2NCT05662228

Therapies for Down Syndrome Regression Disorder

A Phase 2 study testing Lorazepam, Intravenous immunoglobulin (IVIG) and Tofacitinib in people with Down Syndrome and Regression, run by University of Colorado, Denver at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 8 to 30 years
Conditions the study is for
Down Syndrome, Regression
What is being tested?
Lorazepam, Intravenous immunoglobulin (IVIG) and Tofacitinib
Could I receive a placebo?
No, everyone receives an active treatment
How many people
66 participants
Where
2 sitesUnited States
Study dates
29 Jun 2023to 28 May 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 8 to 30 years
  • All sexes
  • No healthy volunteers
  • Child, Adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
Show all 38Show fewer
  • 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.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Children's Hospital Colorado

    Aurora, Colorado, 80045

  • Children's Hospital Los Angeles

    Los Angeles, California, 90027

Other trials in United States

About this study

Official title: Mechanistic Investigation of Therapies for Down Syndrome Regression Disorder

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.

Read the 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.
Being tested
Lorazepam, Intravenous immunoglobulin (IVIG), Tofacitinib
Keywords
Catatonia, Autoimmune disorder, Sleep, Loss of skills, Autoimmune Encephalopathy
Medical subject headings
Down Syndrome, Catatonia, Autoimmune Diseases, Autoimmune Diseases of the Nervous System

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LorazepamDrug

    Also called Ativan

    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.

  • Intravenous immunoglobulin (IVIG)Drug

    Also called Gammagard Liquid (immune globulin infusion [human] 10%)

    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.

  • TofacitinibDrug

    Also called Xeljanz

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

Study groups in NCT05662228
Study groupRoleWhat they receive
LorazepamExperimentalParticipants will receive lorazepam as an oral pill three times daily for 12 weeks as well as titration doses for an additional 4 weeks (approximately).
Receives: Drug: Lorazepam
Intravenous immunoglobulin (IVIG)ExperimentalParticipants will receive 4 doses of IVIG treatment over 12 weeks.
Receives: Drug: Intravenous immunoglobulin (IVIG)
TofacitinibExperimentalTofacitinib will be administered as an oral pill at 5 mg twice daily over the 12-week study.
Receives: Drug: Tofacitinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: Baseline to 14 weeks

Secondary outcomes (7)

  1. Change in catatonia by overall score in BFCRS.

    Change in overall score in the Bush-Francis Catatonia Rating Scale (BFCRS) between baseline and 12 weeks within or between treatment arms. A decrease in score indicates an improved performance.

    Measured: Baseline to 12 weeks

  2. Time to complete 25-Foot Walk assessment.

    Change in the time it takes to complete walking 25 feet between baseline to 12 weeks. A decrease in score indicates an improved performance.

    Measured: Baseline to 12 weeks

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

    Using NEPSY-II to measure change in total number of errors between both car and motorcycle trials. A decrease in score indicates an improved performance.

    Measured: Baseline to 12 weeks

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

    Change in total number or words used in a guided language sample. An increase in score indicates improvement.

    Measured: Baseline to 12 weeks

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

    Change in standard scores for at least one domain in the Vineland Adaptive Behavior Scales-3 (VABS-3) between baseline and 12 weeks within or between treatment arms. An increase in standard score by domain indicates improvement.

    Measured: Baseline to 12 weeks

  6. Change in family impact score as measured by summary score on PedsQL Family Impact Score.

    Change in the Pediatric Quality of Life Inventory (PedsQL) within or between treatment arms. An increase in summary score indicates improvement.

    Measured: Baseline to 12 weeks

  7. Change in quality of life score as measured by PedsQL summary score.

    Change in the Pediatric Quality of Life Inventory (PedsQL) summary score within or between treatment arms. An increase in summary score indicates improvement.

    Measured: Baseline to 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Dec 2022
  2. Study start29 Jun 2023
  3. Primary completion5 May 2026
  4. Study completion28 May 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
We will use covariate-adaptive randomization to assign participants to one of three treatment arms while accounting for sex, age, and other medical history.
Masking
None (open label)
Enrolment
66 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05662228
Sponsor's protocol ID
22-1992
Status last verified
Aug 2026
First submitted
8 Dec 2022
Last updated
3 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: De-identified participant data will be made available for all primary outcome measures.

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lorazepam, Intravenous immunoglobulin (IVIG) and Tofacitinib in people with Down Syndrome and Regression, run by University of Colorado, Denver at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 3 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Comparison of number and severity of all adverse events. (time frame: Baseline to 14 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05662228.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Sep 2026.

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