Telomere Biology DisordersPhase 1NCT06817590
Nucleoside Therapy in Patients With Telomere Biology Disorders
A Phase 1 study testing deoxycytidine and deoxythymidine in people with Telomere Biology Disorders and Dyskeratosis Congenita, run by Suneet Agarwal at 1 site in United States.
Trial summary
The goal of this clinical trial is to learn if a combination therapy of deoxycytidine (dC) plus deoxythymidine (dT) is safe in patients with telomere biology disorders. The main questions it aims to answer are: Is the therapy safe with tolerable side effects in patients with telomere biology disorders? Are problems… Read more about this study
- Who is it for?
- Ages 1 year to 70 years
- Conditions the study is for
- Telomere Biology Disorders, Dyskeratosis Congenita, Revesz Syndrome
- What is being tested?
- deoxycytidine and deoxythymidine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- 29 Sep 2025to Jun 2029
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
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 1 year to 70 years
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age ≥ 1 year and ≤ 70 years
- Karnofsky performance status ≥ 50 for participants ≥16 years of age and Lansky performance status ≥ 50 for participants <16 years of age
- Diagnosis requirement. Participants must meet at least one of the following requirements for a diagnosis of a telomere biology disorder:
- Age-adjusted mean telomere length < 1%ile in peripheral blood lymphocytes by flow cytometry-fluorescence in situ hybridization (flow-FISH), as reported by a Clinical Laboratory Improvement Amendments (CLIA)-approved laboratory
- OR
- Pathogenic or likely pathogenic variant(s) in one of the follow telomere biology associated genes: DKC1, TERC, TERT, NOP10, NHP2, WRAP53/TCAB1, TINF2, CTC1, RTEL1, ACD, PARN, NAF1, STN1, ZCCHC8, POT1, RPA1, DCLRE1B, TYMS, as reported by a CLIA-approved laboratory.
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- Participants must exhibit at least one active clinical manifestation associated with a telomere biology disorder, in the judgment of the PI, which includes but is not limited to the following: one or more peripheral blood cytopenias, bone marrow hypocellular for age, pulmonary abnormalities, liver abnormalities, gastrointestinal bleeding, immunodeficiency or immune dysregulation, ophthalmologic abnormalities, or neurologic abnormalities.
- Participants must be able to take enteral liquids by mouth or enteral feeding tube.
- Female participants who are sexually active and could become pregnant must use two effective methods of contraception, at least one of which must be considered a highly effective method.
- Participants (or parent/legally authorized representative for minors) must demonstrate the ability to understand and willingness to provide informed consent, which will be documented using an institutionally approved informed consent procedure.
Who cannot join
- Participants must not have very severe aplastic anemia necessitating bone marrow transplant at the time of enrollment. Very severe aplastic anemia is defined by the presence of at least 2 of the following: ANC <200 cells/microliter, platelets <20,000 cells/microliter, absolute reticulocyte count <40,000 cells/microliter. If individuals with very severe aplastic anemia are not expected to undergo bone marrow transplant either due to the lack of an acceptable donor or medical co-morbidities and otherwise meet the inclusion/exclusion criteria, then they would be eligible for enrollment in this trial.
- Participants must not otherwise be expected to undergo bone marrow transplantation within 6 months of enrollment.
- Participants must not be taking concurrent medications intended to improve hematopoiesis such as androgens or growth factors, including granulocyte colony stimulating factor, erythropoietin, or thrombopoietin mimetics. If any of these therapies were taken previously, patients must wait 30 days after cessation of the therapy before enrollment on this trial.
- Participants must not have chronic diarrhea or an average baseline stool output of more than 4 stools per day.
- Participants must not have gastrointestinal disorders that may impair enteral absorption of dC/dT, such as inflammatory bowel disease or short bowel syndrome.
- Participants must not have chronic kidney disease with an estimated glomerular filtration rate < 60 mL/min/1.73 m2.
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- Participants must not be on other medications or study agents or have other uncontrolled intercurrent illness that could interfere with study interpretation, in the opinion of the study Principal Investigator (PI)
- Participants must not have high-risk myelodysplastic syndrome or leukemia or other active malignancy.
- Pregnant individuals will not be eligible for enrollment given the physiological changes in blood counts that occur during pregnancy.
- Breastfeeding mothers will not be eligible for enrollment due to the unknown risk to nursing infants.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Boston Childrens Hospital
Boston, Massachusetts, 02115
Helen Reed, MD, MPH, 857-218-4578, helen.reed@childrens.harvard.edu
Brichelle Pena, BS, 617-919-1857, elizabeth.korn@childrens.harvard.edu
About this study
The goal of this clinical trial is to learn if a combination therapy of deoxycytidine (dC) plus deoxythymidine (dT) is safe in patients with telomere biology disorders. The main questions it aims to answer are:
- Is the therapy safe with tolerable side effects in patients with telomere biology disorders?
- Are problems with the bone marrow or blood or lungs changed after 6 months of dC+dT treatment in patients with telomere biology disorders?
Read more
Participants will:
- Take study drug by mouth three times daily for 24 weeks
- Make approximately 2 visits to Boston Children's Hospital during the 24 weeks: once at the beginning of treatment and once at the end of treatment.
- Go to a lab for a blood draw an additional 6 times during treatment.
- Have 9 phone calls with a research nurse, including one 4 weeks after treatment ends.
- Keep a diary to track doses of study drug that were taken or missed.
Read the detailed description
This is an investigator-initiated, single-arm, single-center phase 1 clinical trial investigating nucleoside therapy in patients telomere biology disorder (TBDs). TBDs are a group of rare, inherited conditions characterized by critically short telomeres which can limit cellular replication resulting in a wide spectrum of clinical manifestations. From a hematologic standpoint, patients with TBDs often present with bone marrow failure. Therapy options for bone marrow failure for patients with TBDs are limited to androgen therapy and hematopoietic cell transplantation, which are associated with significant challenges and toxicities. From a pulmonary standpoint, patients with TBDs can present with low oxygen levels due to hepatopulmonary syndrome or lung fibrosis, which requires organ transplantation. New therapeutic approaches are needed in patients with an underlying TBD. Recent studies emerging from multiple independent human genetic studies have established a critical role for deoxythymidine (dT) metabolism in human telomere maintenance and demonstrated that upregulation of nucleotide metabolism by dT supplementation in vitro led to telomere elongation. The goals of this trial are to (1) assess the safety and tolerability of enteral nucleoside therapy in patients with TBDs and (2) explore the clinical and biologic effects of enteral nucleoside therapy in patients with TBDs. A total of 36 pediatric and adult patients with a diagnosis of a TBD will be enrolled at Boston Children's Hospital. Patients will receive enteral nucleoside therapy for a total of 24 weeks. Drug diary reviews and safety and tolerability assessments will be conducted on a weekly basis during an initial dose-escalation phase (4 weeks) and then monthly until study treatment completion at week 24. Pharmacokinetic studies will be conducted on a subset of participants. Additionally, changes in lymphocyte telomere lengths, peripheral blood counts, bone marrow cellularity, clonal hematopoiesis, pulmonary function tests, and chest CT imaging may be explored pre- and post-treatment.
- Conditions
- Telomere Biology Disorders, Dyskeratosis Congenita, Revesz Syndrome, Hoyeraal Hreidarsson Syndrome, Telomere Biology Disorders With Bone Marrow Failure, Interstitial Lung Disease Due to Systemic Disease (Telomere Biology Disorder)
- Being tested
- deoxycytidine, deoxythymidine
- Keywords
- nucleoside, phase I, deoxycytidine, deoxythymidine, telomere biology disorders, safety, tolerability, pharmacokinetics, telomere lengths, bone marrow, clonal hematopoiesis, bone marrow failure, pulmonary fibrosis
- Medical subject headings
- Dyskeratosis Congenita, Revesz Debuse syndrome, Hoyeraal Hreidarsson syndrome, Pulmonary Fibrosis, Bone Marrow Failure Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
deoxycytidineDrug
Also called dC
Oral administration, in combination with deoxythymidine
deoxythymidineDrug
Also called thymidine, dT
Oral administration, in combination with deoxycytidine
| Study group | Role | What they receive |
|---|---|---|
| dC/dT | Experimental | Participants will take study therapy three times daily over 24 weeks with dose escalation. Receives: Drug: deoxycytidine; Drug: deoxythymidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of treatment-related diarrhea [Tolerability]
Proportion of study participants with grade 3 or higher treatment-related diarrhea refractory to dose adjustments
Measured: 8 weeks from study drug initiation
Incidence of treatment-related adverse events [Safety]
Proportion of patients with grade 3 or higher treatment-related adverse events refractory to dose adjustments
Measured: 8 weeks from study drug initiation
Secondary outcomes (7)
Change in hemoglobin
Change in hemoglobin (in grams per deciliter)
Measured: From pre-treatment baseline to end of treatment
Change in platelet count
Change in platelet count (in thousands of cells per microliter)
Measured: From pre-treatment baseline to end of treatment
Change in absolute neutrophil count
Change in absolute neutrophil count (in thousands of cells per microliter)
Measured: From pre-treatment baseline to end of treatment
Maximal plasma concentration [Cmax] of dC
Maximal plasma concentration [Cmax] of dC will be obtained during pharmacokinetic profiling of dC at starting dose and maximum dose in some subjects
Measured: 24 weeks
Maximal plasma concentration [Cmax] of dT
Maximal plasma concentration [Cmax] of dT will be obtained during pharmacokinetic profiling of dT at starting dose and maximum dose in some subjects
Measured: 24 weeks
Plasma half-life [T1/2] of dC
Plasma half-life [T1/2] of dC will be obtained during pharmacokinetic profiling of dC at starting dose and maximum dose in some subjects
Measured: 24 weeks
Plasma half-life [T1/2] of dT
Plasma half-life [T1/2] of dT will be obtained during pharmacokinetic profiling of dC at starting dose and maximum dose in some subjects
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Feb 2025
- Study start29 Sep 2025
- Primary completionJun 2028 (estimated)
- Study completionJun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Telomere Biology DisordersStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Suneet Agarwal
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Suneet Agarwal, Boston Children's Hospital
- Investigators
- Helen Reed, MD, MPH, Principal investigator, Boston Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06817590
- Sponsor's protocol ID
- IRB-P00049530
- Status last verified
- Sep 2025
- First submitted
- 30 Jan 2025
- Last updated
- 4 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mannherz W, Agarwal S. Thymidine nucleotide metabolism controls human telomere length. Nat Genet. 2023 Apr;55(4):568-580. doi: 10.1038/s41588-023-01339-5. Epub 2023 Mar 23.
PubMed 36959362
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nucleoside Therapy in Patients With Telomere Biology Disorders
- ClinicalTrials.gov ID
- NCT06817590
- Acronym / sponsor ID
- IRB-P00049530
- Conditions
- Telomere Biology Disorders, Dyskeratosis Congenita, Revesz Syndrome, Hoyeraal Hreidarsson Syndrome, Telomere Biology Disorders With Bone Marrow Failure, Interstitial Lung Disease Due to Systemic Disease (Telomere Biology Disorder)
- Keywords
- nucleoside, phase I, deoxycytidine, deoxythymidine, telomere biology disorders, safety, tolerability, pharmacokinetics
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Suneet AgarwalUniversity, hospital or other
- Study start
- 29 Sep 2025 (actual)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Jun 2029 (estimated)
- First posted
- 10 Feb 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The goal of this clinical trial is to learn if a combination therapy of deoxycytidine (dC) plus deoxythymidine (dT) is safe in patients with telomere biology disorders. The main questions it aims to answer are:
- Is the therapy safe with tolerable side effects in patients with telomere biology disorders?
- Are problems with the bone marrow or blood or lungs changed after 6 months of dC+dT treatment in patients with telomere biology disorders?
Participants will:
- Take study drug by mouth three times daily for 24 weeks
- Make approximately 2 visits to Boston Children's Hospital during the 24 weeks: once at the beginning of treatment and once at the end of treatment.
- Go to a lab for a blood draw an additional 6 times during treatment.
- Have 9 phone calls with a research nurse, including one 4 weeks after treatment ends.
- Keep a diary to track doses of study drug that were taken or missed.
Detailed description
This is an investigator-initiated, single-arm, single-center phase 1 clinical trial investigating nucleoside therapy in patients telomere biology disorder (TBDs). TBDs are a group of rare, inherited conditions characterized by critically short telomeres which can limit cellular replication resulting in a wide spectrum of clinical manifestations. From a hematologic standpoint, patients with TBDs often present with bone marrow failure. Therapy options for bone marrow failure for patients with TBDs are limited to androgen therapy and hematopoietic cell transplantation, which are associated with significant challenges and toxicities. From a pulmonary standpoint, patients with TBDs can present with low oxygen levels due to hepatopulmonary syndrome or lung fibrosis, which requires organ transplantation. New therapeutic approaches are needed in patients with an underlying TBD. Recent studies emerging from multiple independent human genetic studies have established a critical role for deoxythymidine (dT) metabolism in human telomere maintenance and demonstrated that upregulation of nucleotide metabolism by dT supplementation in vitro led to telomere elongation. The goals of this trial are to (1) assess the safety and tolerability of enteral nucleoside therapy in patients with TBDs and (2) explore the clinical and biologic effects of enteral nucleoside therapy in patients with TBDs. A total of 36 pediatric and adult patients with a diagnosis of a TBD will be enrolled at Boston Children's Hospital. Patients will receive enteral nucleoside therapy for a total of 24 weeks. Drug diary reviews and safety and tolerability assessments will be conducted on a weekly basis during an initial dose-escalation phase (4 weeks) and then monthly until study treatment completion at week 24. Pharmacokinetic studies will be conducted on a subset of participants. Additionally, changes in lymphocyte telomere lengths, peripheral blood counts, bone marrow cellularity, clonal hematopoiesis, pulmonary function tests, and chest CT imaging may be explored pre- and post-treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| dC/dT | Experimental | Drug: deoxycytidine, Drug: deoxythymidineParticipants will take study therapy three times daily over 24 weeks with dose escalation. |
Who may qualify
- Ages
- 1 year to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (10 listed)
- Age ≥ 1 year and ≤ 70 years
- Karnofsky performance status ≥ 50 for participants ≥16 years of age and Lansky performance status ≥ 50 for participants <16 years of age
- Diagnosis requirement. Participants must meet at least one of the following requirements for a diagnosis of a telomere biology disorder:
- OR
- Participants must exhibit at least one active clinical manifestation associated with a telomere biology disorder, in the judgment of the PI, which includes but is not limited to the following: one or more peripheral blood cytopenias, bone marrow hypocellular for age, pulmonary abnormalities, liver abnormalities, gastrointestinal bleeding, immunodeficiency or immune dysregulation, ophthalmologic abnormalities, or neurologic abnormalities.
Key exclusion criteria (10 listed)
- Participants must not have very severe aplastic anemia necessitating bone marrow transplant at the time of enrollment. Very severe aplastic anemia is defined by the presence of at least 2 of the following: ANC <200 cells/microliter, platelets <20,000 cells/microliter, absolute reticulocyte count <40,000 cells/microliter. If individuals with very severe aplastic anemia are not expected to undergo bone marrow transplant either due to the lack of an acceptable donor or medical co-morbidities and otherwise meet the inclusion/exclusion criteria, then they would be eligible for enrollment in this trial.
- Participants must not otherwise be expected to undergo bone marrow transplantation within 6 months of enrollment.
- Participants must not be taking concurrent medications intended to improve hematopoiesis such as androgens or growth factors, including granulocyte colony stimulating factor, erythropoietin, or thrombopoietin mimetics. If any of these therapies were taken previously, patients must wait 30 days after cessation of the therapy before enrollment on this trial.
- Participants must not have chronic diarrhea or an average baseline stool output of more than 4 stools per day.
- Participants must not have gastrointestinal disorders that may impair enteral absorption of dC/dT, such as inflammatory bowel disease or short bowel syndrome.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| deoxycytidineAlso: dCOral administration, in combination with deoxythymidine | Drug | dC/dT |
| deoxythymidineAlso: thymidine, dTOral administration, in combination with deoxycytidine | Drug | dC/dT |
Primary outcome
Incidence of treatment-related diarrhea [Tolerability]
Time frame: 8 weeks from study drug initiation
Proportion of study participants with grade 3 or higher treatment-related diarrhea refractory to dose adjustments
Incidence of treatment-related adverse events [Safety]
Time frame: 8 weeks from study drug initiation
Proportion of patients with grade 3 or higher treatment-related adverse events refractory to dose adjustments
7 secondary outcomes
Change in hemoglobin
Time frame: From pre-treatment baseline to end of treatment
Change in platelet count
Time frame: From pre-treatment baseline to end of treatment
Change in absolute neutrophil count
Time frame: From pre-treatment baseline to end of treatment
Maximal plasma concentration [Cmax] of dC
Time frame: 24 weeks
Maximal plasma concentration [Cmax] of dT
Time frame: 24 weeks
Plasma half-life [T1/2] of dC
Time frame: 24 weeks
Plasma half-life [T1/2] of dT
Time frame: 24 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2026.
- Background: PubMed 36959362Mannherz W, Agarwal S. Thymidine nucleotide metabolism controls human telomere length. Nat Genet. 2023 Apr;55(4):568-580. doi: 10.1038/s41588-023-01339-5. Epub 2023 Mar 23.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Helen Reed, MD, MPH principal investigator
Boston Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing deoxycytidine and deoxythymidine in people with Telomere Biology Disorders and Dyskeratosis Congenita, run by Suneet Agarwal at 1 site 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 10 inclusion and 10 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: looking for participants now, as of the sponsor's last update on 4 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Helen Reed, MD, MPH (857-218-4578, helen.reed@childrens.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of treatment-related diarrhea [Tolerability] (time frame: 8 weeks from study drug initiation). The study lists 2 primary outcomes in all. 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 NCT06817590, which also lists 1 linked publication.
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 4 Aug 2026.