NCOR Gene MutationsPhase 2/3NCT06678685
Spironolactone Improved Children With Gene Mutations Related to NCOR
A Phase 2/3 study testing .spironolactone in people with NCOR Gene Mutations and Spironolactone, run by Qilu Hospital of Shandong University at 1 site in China.
Trial summary
MECP2, a key transcriptional regulator, has been shown to interact with the NCOR1/2 complex to modulate gene expression. Specifically, MECP2 recruits the NCOR complex to specific genomic loci, facilitating histone deacetylation and chromatin remodeling, which are essential for the proper regulation of genes involved… Read more about this study
- Who is it for?
- Ages 3 to 10 years
- Conditions the study is for
- NCOR Gene Mutations, Spironolactone, ASD
- What is being tested?
- .spironolactone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteChina
- Study dates
- 30 Oct 2024to 30 Dec 2027
- Phase
- Phase 2/3
- 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 3 to 10 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- ADOS-2 diagnostic criteria for autistic children
- Patients with NCOR related gene mutation detected by whole exon test;
- Age: 3-10 years old;
- The subject and (or) guardian sign the informed consent, agreeing that the researcher will cooperate with the clinical trial process and collect clinical data and peripheral blood and urine samples;
Who cannot join
- have other pathogenic mutations (confidence higher than the NCOR related mutation);
- Boys over 10 years old;
- Allergic to spironolactone, used spironolactone one month before enrollment;
- Hyperkalemia, serum potassium concentration > 5.5mmol/L;
- Renal insufficiency;
- Used related drugs one month before enrollment: potassium supplement, angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, digoxin, coletenamine, acetylsalicylic acid, abiraterone;
- Fever (body temperature above 37.3°);
- Clinically significant metabolic, hematological, liver, immune, urological, endocrine, neurological, pulmonary, psychiatric, skin, allergic, renal, or other major conditions in the determination of ASD that may affect the interpretation of study findings or patient safety.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
China1 site, 1 recruiting
- Recruiting
Qilu Hospital of Shandong University
Jinan, Shandong, 250012
Aihua cao Cao, 18560086317, qlyyebk@163.com
About this study
Official title: An Exploratory Study of Spironolactone Tablets for the Treatment of Children With Gene Mutations Related to NCOR
MECP2, a key transcriptional regulator, has been shown to interact with the NCOR1/2 complex to modulate gene expression. Specifically, MECP2 recruits the NCOR complex to specific genomic loci, facilitating histone deacetylation and chromatin remodeling, which are essential for the proper regulation of genes involved in synaptic function and neuronal maturation. Disruptions in the MECP2-NCOR interaction have been implicated in neurodevelopmental disorders, including Rett syndrome and autism spectrum disorder (ASD), highlighting the collaborative role of MECP2 and the NCOR1/2 complex in maintaining neuronal homeostasis.
Building on this, NCOR1/2 constitutes the NCOR complex,interacts with many different nuclear receptors to produce special physiological effects. The receptors further recruit epigenome-modifying enzymes that are involved in the transcription of multiple genes involved in neurotransmission and synaptic plasticity. Studies of mice with gene knockout and autistic with NCOR mutations have found that both exhibit clinical symptoms characteristic of ASD, such as deficits in social interaction, spatial learning, and impaired recognition memory. Further study revealed that the cause was the hyperexcitability of GABAergic neurons in the lateral hypothalamus (LH) due to the NCOR1/2 defect, which impaired synaptic plasticity in the hippocampal CA3 region through the single synaptic LHGABA-CA3 neural projection, and thus exhibited learning/memory impairment. Therefore, drugs that affect the NCOR receptor can improve learning/memory impairment by affecting GABA neurons. Spironolactone is a widely used diuretic with good safety. Spironolactone is widely used in the treatment of hypertension, edema, and anti-androgen therapy in children. Spironolactone is currently under investigation as a potential treatment for children with NCOR gene mutations. Preclinical studies have demonstrated that spironolactone can ameliorate ASD-related symptoms in NCOR mutant mice, including reduced sensorimotor capacity, learning disability, and impaired working memory. Furthermore, the efficacy of related diuretics in the treatment of ASD has been demonstrated clinically. Therefore, spironolactone may represent a novel therapeutic target for patients with NCOR-related gene mutations in the future.
- Conditions
- NCOR Gene Mutations, Spironolactone, ASD
- Being tested
- .spironolactone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
.spironolactoneDrug
In the first week, the starting dose is 2mg/Kg per body weight once a day, taken with food at lunch every day, and subsequently adjusted according to the situation. If the patient's serum potassium is ≤5.0 mEq/L and the patient's serum creatinine is ≤2.5 mg/dL, treatment should be initiated with 25 mg spironolactone once daily. Increased to 100mg after remission. If the results are not obvious in the first month, increase the drug dose to 3mg/Kg.
| Study group | Role | What they receive |
|---|---|---|
| spironolactone treatment | Experimental | Not described Receives: Drug: .spironolactone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV)
Scores range from 40 to 130, with higher scores representing higher intelligence
Measured: 1. Baseline 2. At the end of Cycle 1 (each cycle is 45 days)
Autism Diagnostic Observation Scale-2
The score ranges from 0 to 9, with higher scores indicating more severe autism
Measured: 1. Baseline ;2. At the end of Cycle 1 (each cycle is 45 days)
Secondary outcomes (7)
Blood pressure
Including systolic and diastolic blood pressure
Measured: 1. Baseline 2. At the end of Cycle 1 (each cycle is 60 days) 3.At the end of Cycle 2 (each cycle is 60 days)
The Score of Autism Behavior Checklist (ABC)
The Autism Behavior Checklist (ABC)63 was administered to screen for autism spectrum traits. Parents rated 57 items across five domains: Sensory, Relating, Body and Object Use, Language, and Social/Self-Help Skills. Total scores were classified to indicate the severity of autistic features.
Measured: 1. Baseline 2. At the end of Cycle 1 (each cycle is 45 days)
The Score of Childhood Autism Rating Scale (CARS)
The Childhood Autism Rating Scale (CARS)62 provides a clinician-completed global evaluation of autism severity; total scores categorize individuals as non-autistic (<30), mildly-to-moderately autistic (30-36.5), or severely autistic (≥37).
Measured: 1. Baseline ;2. At the end of Cycle 1 (each cycle is 45 days)
the score of Vineland Adaptive Behavior Scales, Third Edition (Vineland-3)
Adaptive functioning was evaluated using the Vineland Adaptive Behavior Scales, Third Edition (Vineland-3) 64, which assesses Motor Skills (MOT), Communication (COM), Daily Living Skills (DLS), and Socialization (SOC). Parent-reported scores were stratified into Very Superior (130-140), Superior (115-129), Average (86-114), Low (71-85), or Very Low (≤70)
Measured: 1. Baseline ;2. At the end of Cycle 1 (each cycle is 45 days)
the score of Chinese Communicative Development Inventory (CDI)
Language development was analyzed using the Chinese Communicative Development Inventory (CDI)65, a parent-reported questionnaire that quantifies expressive/receptive vocabulary, syntactic complexity, and gestural communication across multiple subdomains (e.g., verbs, spatial terms, phrases).
Measured: 1. Baseline 2. At the end of Cycle 1 (each cycle is 45 days)
the score of Conners Parent Symptom Questionnaire (CPRS)
Behavioral challenges were assessed using the Conners Parent Symptom Questionnaire (CPRS)66, which evaluates impulsivity-hyperactivity, conduct problems, learning difficulties, psychosomatic symptoms, and anxiety. Total scores were categorized as Normal, Borderline, or Abnormal.
Measured: 1. Baseline 2. At the end of Cycle 1 (each cycle is 45 days)
The score of School-Age Children's Behavioral Rating Scale of Executive Function
The School-Age Children's Behavioral Rating Scale of Executive Function evaluated multiple cognitive control processes, including Initiation (ability to begin tasks independently), Working Memory (capacity to hold and manipulate information), Inhibition (control over impulsive responses), and Organization (skills in structuring tasks and materials). Higher scores on this scale indicate better executive function performance in daily activities.
Measured: 1. Baseline 2. At the end of Cycle 1 (each cycle is 45 days)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Nov 2024
- Study start30 Oct 2024
- Primary completion30 Dec 2026 (estimated)
- Study completion30 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NCOR Gene MutationsStudies of the same condition, open and under way.
- More trials run by Qilu Hospital of Shandong UniversityThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 2 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Qilu Hospital of Shandong University
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06678685
- Sponsor's protocol ID
- QL000004
- Status last verified
- Oct 2025
- First submitted
- 27 Oct 2024
- Last updated
- 18 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Exploratory Study of Spironolactone Tablets for the Treatment of Children With Gene Mutations Related to NCOR
- ClinicalTrials.gov ID
- NCT06678685
- Acronym / sponsor ID
- QL000004
- Conditions
- NCOR Gene Mutations, Spironolactone, ASD
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 2 participants (estimated)
- Lead sponsor
- Qilu Hospital of Shandong UniversityUniversity, hospital or other
- Study start
- 30 Oct 2024 (actual)
- Primary completion
- 30 Dec 2026 (estimated)
- Study completion
- 30 Dec 2027 (estimated)
- First posted
- 7 Nov 2024 (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.
MECP2, a key transcriptional regulator, has been shown to interact with the NCOR1/2 complex to modulate gene expression. Specifically, MECP2 recruits the NCOR complex to specific genomic loci, facilitating histone deacetylation and chromatin remodeling, which are essential for the proper regulation of genes involved in synaptic function and neuronal maturation. Disruptions in the MECP2-NCOR interaction have been implicated in neurodevelopmental disorders, including Rett syndrome and autism spectrum disorder (ASD), highlighting the collaborative role of MECP2 and the NCOR1/2 complex in maintaining neuronal homeostasis.
Building on this, NCOR1/2 constitutes the NCOR complex,interacts with many different nuclear receptors to produce special physiological effects. The receptors further recruit epigenome-modifying enzymes that are involved in the transcription of multiple genes involved in neurotransmission and synaptic plasticity. Studies of mice with gene knockout and autistic with NCOR mutations have found that both exhibit clinical symptoms characteristic of ASD, such as deficits in social interaction, spatial learning, and impaired recognition memory. Further study revealed that the cause was the hyperexcitability of GABAergic neurons in the lateral hypothalamus (LH) due to the NCOR1/2 defect, which impaired synaptic plasticity in the hippocampal CA3 region through the single synaptic LHGABA-CA3 neural projection, and thus exhibited learning/memory impairment. Therefore, drugs that affect the NCOR receptor can improve learning/memory impairment by affecting GABA neurons. Spironolactone is a widely used diuretic with good safety. Spironolactone is widely used in the treatment of hypertension, edema, and anti-androgen therapy in children. Spironolactone is currently under investigation as a potential treatment for children with NCOR gene mutations. Preclinical studies have demonstrated that spironolactone can ameliorate ASD-related symptoms in NCOR mutant mice, including reduced sensorimotor capacity, learning disability, and impaired working memory. Furthermore, the efficacy of related diuretics in the treatment of ASD has been demonstrated clinically. Therefore, spironolactone may represent a novel therapeutic target for patients with NCOR-related gene mutations in the future.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| spironolactone treatment | Experimental | Drug: .spironolactone |
Who may qualify
- Ages
- 3 to 10 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- ADOS-2 diagnostic criteria for autistic children
- Patients with NCOR related gene mutation detected by whole exon test;
- Age: 3-10 years old;
- The subject and (or) guardian sign the informed consent, agreeing that the researcher will cooperate with the clinical trial process and collect clinical data and peripheral blood and urine samples;
Key exclusion criteria (8 listed)
- have other pathogenic mutations (confidence higher than the NCOR related mutation);
- Boys over 10 years old;
- Allergic to spironolactone, used spironolactone one month before enrollment;
- Hyperkalemia, serum potassium concentration > 5.5mmol/L;
- Renal insufficiency;
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 |
|---|---|---|
| .spironolactoneIn the first week, the starting dose is 2mg/Kg per body weight once a day, taken with food at lunch every day, and subsequently adjusted according to the situation. If the patient's serum potassium is ≤5.0 mEq/L and the patient's serum creatinine is ≤2.5 mg/dL, treatment should be initiated with 25 mg spironolactone once daily. Increased to 100mg after remission. If the results are not obvious in the first month, increase the drug dose to 3mg/Kg. | Drug | spironolactone treatment |
Primary outcome
Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV)
Time frame: 1. Baseline 2. At the end of Cycle 1 (each cycle is 45 days)
Scores range from 40 to 130, with higher scores representing higher intelligence
Autism Diagnostic Observation Scale-2
Time frame: 1. Baseline ;2. At the end of Cycle 1 (each cycle is 45 days)
The score ranges from 0 to 9, with higher scores indicating more severe autism
7 secondary outcomes
Blood pressure
Time frame: 1. Baseline 2. At the end of Cycle 1 (each cycle is 60 days) 3.At the end of Cycle 2 (each cycle is 60 days)
The Score of Autism Behavior Checklist (ABC)
Time frame: 1. Baseline 2. At the end of Cycle 1 (each cycle is 45 days)
The Score of Childhood Autism Rating Scale (CARS)
Time frame: 1. Baseline ;2. At the end of Cycle 1 (each cycle is 45 days)
the score of Vineland Adaptive Behavior Scales, Third Edition (Vineland-3)
Time frame: 1. Baseline ;2. At the end of Cycle 1 (each cycle is 45 days)
the score of Chinese Communicative Development Inventory (CDI)
Time frame: 1. Baseline 2. At the end of Cycle 1 (each cycle is 45 days)
the score of Conners Parent Symptom Questionnaire (CPRS)
Time frame: 1. Baseline 2. At the end of Cycle 1 (each cycle is 45 days)
The score of School-Age Children's Behavioral Rating Scale of Executive Function
Time frame: 1. Baseline 2. At the end of Cycle 1 (each cycle is 45 days)
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 18 May 2026.
- Individual participant dataSharing planned: Yes
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing .spironolactone in people with NCOR Gene Mutations and Spironolactone, run by Qilu Hospital of Shandong University at 1 site in China.
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 4 inclusion and 8 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 18 May 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 China. 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 Cao Aihua Qilu Hospital of Shandong University (18560086317, qlyyebk@163.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Wechsler Intelligence Scale for Children, Fourth Edition (WISC-IV) (time frame: 1. Baseline 2. At the end of Cycle 1 (each cycle is 45 days)). 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?
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 18 May 2026.