Spironolactone Improved Children With NCOR Mutations

Shandong University

Status and phase: Not yet enrolling; Phase 3; Phase 2

Conditions: NCOR Gene Mutations; Spironolactone; ASD

Treatments: Drug: .spironolactone

Study type: Interventional

Funder types: Other

Identifiers

NCT06678685

QL000004

Details and patient eligibility

About

NCOR1/2 constitutes the NCOR complex, which interacts with many different nuclear receptors to produce special physiological effects. These 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 patients 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. It is widely used in the treatment of hypertension, edema and anti-androgen therapy in children. In this study, spironolactone is one of the most popular drugs used to treat children with NCOR gene mutation. In our previous animal experiments, we found that spironolactone could treat NCOR mutant mice and improve ASD-related symptoms, such as reduced sensorimotor capacity, learning disability and impaired working memory; Moreover, the efficacy of related diuretics in the treatment of ASD diseases has been proved clinically. So spironolactone may be a new target for the treatment of NCOR patients in the future.

Enrollment: 3 estimated patients

Sex: All

Ages: 3 to 10 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. ADOS-2 diagnostic criteria for autistic children
2. Patients with NCOR1/2 gene mutation detected by whole exon test;
3. Age: 3-10 years old;
4. 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;

Exclusion criteria

1. have other pathogenic mutations (confidence higher than the NCOR1/2 mutation);
2. Boys over 10 years old;
3. Allergic to spironolactone, used spironolactone one month before enrollment;
4. Hyperkalemia, serum potassium concentration > 5.5mmol/L;
5. Renal insufficiency;
6. Used related drugs one month before enrollment: potassium supplement, angiotensin-converting enzyme inhibitor, angiotensin receptor blocker, digoxin, coletenamine, acetylsalicylic acid, abiraterone;
7. Fever (body temperature above 37.3°);
8. 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 design

Primary purpose: Treatment

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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3 participants in 1 patient group

spironolactone treatment

Experimental group

Treatment:

Drug: .spironolactone