A Phase 2 interventional study of Lorazepam and Intravenous immunoglobulin (IVIG) in Down Syndrome and Regression, sponsored by University of Colorado, Denver. Completed at 2 sites in United States. Open to participants aged 8 Years to 30 Years. Per ClinicalTrials.gov, last updated 2026-09-03.
Sponsored by University of Colorado, Denver · Phase 2, Interventional, and Treatment
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.
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:
438 studies on the registry are indexed under Down Syndrome; 99 are open to participants now.
This study's enrollment of 66 is above the median of 37 across 286 interventional studies indexed under Down Syndrome.
Browse Down Syndrome studies →University of Colorado, Denver is the lead sponsor of 1,543 studies on the registry; 317 are open to participants now.
Of its 147 completed or terminated interventional studies of FDA-regulated products, 92 (63%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
General
Co-occurring Conditions
Medications or Interventions
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Washout period
A planned gap after a treatment, so that its effects can lessen before the study treatment or a study assessment. Ask the study team and the doctor who prescribed it before changing any medicine.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Clinically significant
Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Cancer (malignancy)
Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.
Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Autoimmune disease
A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.
Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Immunosuppression
A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.
Read whether the line is about a condition or about medicines, and which medicines and doses it means.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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
Participants will receive 4 doses of IVIG treatment over 12 weeks.
Drug: Intravenous immunoglobulin (IVIG)
Tofacitinib will be administered as an oral pill at 5 mg twice daily over the 12-week study.
Drug: Tofacitinib
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
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%)
Tofacitinib will be administered as an oral pill at 5 mg twice daily over the 12-week study.
Also known as: Xeljanz
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.
Time frame: Baseline to 14 weeks
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.
Time frame: Baseline to 12 weeks
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.
Time frame: Baseline to 12 weeks
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.
Time frame: Baseline to 12 weeks
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.
Time frame: Baseline to 12 weeks
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.
Time frame: Baseline to 12 weeks
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.
Time frame: Baseline to 12 weeks
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.
Time frame: Baseline to 12 weeks
Change in social interaction as measured by SRS-2 subdomain T-scores.
Change in Social Responsiveness Scale-2 (SRS-2) subdomain treatment T-scores within or between treatment arms. A decrease in score indicates improvement.
Time frame: Baseline to 12 weeks
Change in behavior as measured by DBC-2 T-score.
A statistically significant change in Developmental Behavioral Checklist-2 (DBC-2) T-scores within or between treatment arms. A decrease in score indicates improvement.
Time frame: Baseline to 12 weeks
Change in one or more measures of overall cognitive ability.
A statistically significant change in one or more measures of overall cognitive ability within or between treatment arms. Measures include: * Behavior Rating Inventory of Executive Function, 2nd Edition (BRIEF-2): Change in T-scores. * Down Syndrome Mental Status Exam (DSMSE): Change in Total Memory and Non-Memory Composite score. . * Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associate Learning (PAL) subdomain will be used to measure episodic learning. * CANTAB Spatial Span (SS) will be used to measure spatial processing. * CANTAB Reaction Time Interval (RTI) subdomain will be used to measure processing speed. * Kaufman Brief Intelligence Test-2 Revised (KBIT-2 Revised): Change in Standard Score. * Neuropsychiatric Inventory (NPI): Change in total score.
Time frame: Baseline to 12 weeks
Change in receptive language as measured by PVT raw score.
Change in the raw score of the NIH Toolbox Picture Vocabulary Test (PVT). An increase in score indicates an improved performance.
Time frame: Baseline to 12 weeks
PDFs hosted by the registry, ClinicalTrials.gov.
Plan to share: Yes — De-identified participant data will be made available for all primary outcome measures.
Supporting information: Study protocol, Statistical analysis plan, Informed consent form, 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.
This study is completed, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drugs tested here: Lorazepam · Immunoglobulins, Intravenous · Tofacitinib
University of Colorado, Denver →