Thymidine nucleotide metabolism controls human telomere length.
William Mannherz, Suneet Agarwal
https://pubmed.ncbi.nlm.nih.gov/36959362Actively Recruiting
Phase 1
Age: 1Year - 70Years
All Genders
ID06817590
Nucleoside Therapy in Patients With Telomere Biology Disorders Evaluating Safety and Effects of Oral dC and dT Treatment
Led by Suneet Agarwal · Updated on 2026-03-18
36
Participants Needed
1
Research Sites
52 weeks
Total Duration
On this page
AI-Summary
What this Trial Is About
Researchers are studying the safety and effects of a combination therapy using deoxycytidine (dC) and deoxythymidine (dT) in patients with telomere biology disorders (TBDs). These are rare inherited conditions causing very short telomeres, which can lead to problems like bone marrow failure and lung issues. The trial aims to assess if the therapy is safe and to observe changes in blood and lung health after treatment. Participants will take the study drugs by mouth three times daily for 24 weeks, with a dose escalation during the first 4 weeks. This single-arm phase 1 trial involves about 36 pediatric and adult patients receiving nucleoside therapy at Boston Children's Hospital. Study visits include two in-person visits at the start and end of treatment, plus six blood draws and nine phone calls with a research nurse, including one follow-up call 4 weeks after treatment ends. During the trial, participants will keep a diary to record doses taken or missed, and researchers will monitor safety and tolerability weekly during the initial dose escalation and monthly thereafter. They will evaluate blood counts, bone marrow cellularity, telomere length, lung function, and imaging before and after treatment. The main outcomes include the frequency of treatment-related diarrhea and other adverse events within 8 weeks of starting therapy.
CONDITIONS
Brief Title
Nucleoside Therapy in Patients With Telomere Biology Disorders
Who Can Participate
Age: 1Year - 70Years
All Genders
Eligibility Criteria
You may qualify if you...
- Age 1 year to 70 years
- Karnofsky performance status 50 or higher for participants 16 years and older, Lansky performance status 50 or higher for participants younger than 16 years
- Confirmed diagnosis of a telomere biology disorder by either age-adjusted telomere length below 1st percentile or a pathogenic variant in specific telomere-related genes
- At least one active clinical symptom related to telomere biology disorder such as blood cell deficiency, bone marrow issues, lung or liver abnormalities, immune problems, eye or neurological issues
- Ability to take liquids by mouth or feeding tube
- Female participants capable of pregnancy must use two effective contraception methods, including one highly effective method
- Ability and willingness to provide informed consent
You will not qualify if you...
- Very severe aplastic anemia requiring bone marrow transplant unless transplant not expected due to donor availability or medical reasons
- Expected bone marrow transplant within 6 months
- Currently taking medications to improve blood cell production such as androgens or growth factors; at least 30 days must have passed since stopping such therapies
- Chronic diarrhea or average of more than 4 stools per day
- Gastrointestinal disorders impairing absorption of study drugs, like inflammatory bowel disease or short bowel syndrome
- Chronic kidney disease with estimated glomerular filtration rate below 60 mL/min/1.73 m2
- Use of other medications or illnesses interfering with study interpretation
- High-risk myelodysplastic syndrome, leukemia, or other active cancers
- Pregnancy or breastfeeding mothers not eligible due to risks to infants
AI-Screening
AI-Powered Screening
Complete this quick 3-step screening to check your eligibility
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Your Study Journey
Screening
Duration - 2 to 4 weeks
Participants are screened for eligibility to participate in the trial.
1 visit (in-person)
Run-in Period
Duration - 4 weeks
Participants undergo a dose-escalation phase of oral nucleoside therapy to assess safety and tolerability.
Weekly visits for 4 weeks
Treatment
Duration - 20 weeks
Participants continue oral nucleoside therapy three times daily to evaluate clinical and biologic effects.
Monthly visits for 5 months
Trial Site Locations
Total: 1 location
1
Boston Childrens Hospital
Boston, Massachusetts, United States, 02115
Actively Recruiting
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Research Team
H
Helen Reed, MD, MPH
E
Elizabeth Korn, BS
How is the study designed?
Study Type
INTERVENTIONAL
Masking
NONE
Allocation
NA
Model
SINGLE_GROUP
Primary Purpose
TREATMENT
Number of Arms
1
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