Trial Title:
Effects of Growth Hormone Therapy on Metabolic Function in Fatty Liver Post-Pituitary Adenoma Surgery
NCT ID:
NCT06448195
Condition:
Growth Hormone Treatment
Conditions: Official terms:
Adenoma
Fatty Liver
Hormones
Study type:
Interventional
Study phase:
Phase 4
Overall status:
Recruiting
Study design:
Allocation:
Randomized
Intervention model:
Parallel Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Polyethylene Glycol Somatropin (rDNA origin) Injection
Description:
Specification: 54IU/9.0mg/1.0ml/ bottle Dosage form: injection; Dose: 1mg/ week.
Subcutaneous injection (upper arm, thigh or abdomen periumbilical) for a total course of
6 months, a total of 3 bottles per patient
Arm group label:
Growth hormone treatment group
Other name:
Growth hormone replacement therapy
Summary:
Growth Hormone (GH) is essential for maintaining fat, muscle, bone, and energy balance.
Adult Growth Hormone Deficiency (GHD) affects about 0.3% of adults. GHD, common
post-pituitary tumor surgery or radiotherapy, disrupts lipid metabolism, increasing
triglycerides and low-density lipoprotein cholesterol while decreasing high-density
lipoprotein cholesterol. This is especially severe in GH adenoma patients, whose lipid
metabolism issues worsen post-surgery, increasing the risk of atherosclerosis. Fat
accumulates in the liver first, making liver fat content a key early indicator of
metabolic disorders, which can lead to diabetes and atherosclerosis. Early intervention
is crucial as liver fat deposition in Nonalcoholic Fatty Liver Disease (NAFLD) is
reversible.
Recombinant human growth hormone can treat GHD-related lipid metabolism disorders, but
research on its effects on liver fat in post-surgery GH adenoma patients is limited. The
investigators plan to treat these patients with 1 mg/week of recombinant human growth
hormone for 24 weeks, aiming to normalize insulin-like growth factor-1 levels. Liver fat
content changes will be measured using proton magnetic resonance spectroscopy (1H MRS)
and Fibroscan. Changes in weight, BMI, waist circumference, fasting blood glucose, blood
lipids, and other metabolic factors will also be evaluated to assess treatment efficacy
and safety.
Zhongshan Hospital, affiliated with Fudan University, performs over 300 pituitary tumor
surgeries annually, including 100 GH adenoma cases. The hospital has extensive experience
and can enroll 40 patients. The Endocrinology Department excels in evaluating lipid
metabolism disorders in NAFLD using non-invasive methods. As a major hospital in
Shanghai, it has ample patients to meet study requirements. Detailed exit criteria and
rescue plans have been established to address potential adverse events during the study.
Detailed description:
Growth Hormone (GH) is an important hormone secreted by the pituitary gland and is
essential for maintaining normal fat, muscle, bone content, and energy balance in the
body. The prevalence of adult Growth Hormone Deficiency (GHD) is approximately 0.3% in
adults. When human growth hormone is deficient, lipid metabolism is most prone to
disorder. The study found that blood triglyceride and low-density lipoprotein cholesterol
levels increased in GHD patients, and blood high-density lipoprotein cholesterol levels
decreased. GHD is most common in patients with pituitary tumor after surgery or
radiotherapy, especially in patients with GH adenoma after surgery. The lipid metabolism
disorder is the most serious among all GHD patients because the excessive growth hormone
before surgery has caused a state of severe lipid metabolism disorder, and after surgery,
patients are directly converted to a state of growth hormone deficiency, exacerbating the
lipid metabolism disorder. This disorder will progress from poor to worse, and long-term
follow-up shows a higher likelihood of developing secondary atherosclerotic diseases
post-surgery.
Current studies have shown that when abnormal lipid metabolism occurs in GHD patients,
fat will first accumulate in the liver. Therefore, compared with changes in blood lipid
metabolism indexes and body components, changes in liver fat content can detect abnormal
lipid metabolism earlier. Liver fat deposition, as the initiating factor of systemic
metabolic disorders, is involved in the occurrence and development of diabetes and
atherosclerotic diseases. Currently, it is considered that the fat deposition in
Nonalcoholic Fatty Liver Disease (NAFLD) is reversible. Therefore, it is particularly
urgent to conduct very early intervention for GHD patients with pituitary GH adenoma
after operation to block the occurrence of subsequent metabolic adverse events.
It has been reported that recombinant human growth hormone can be used in the treatment
of abnormal lipid metabolism due to GHD, but at present, there is a lack of relevant
studies on recombinant human growth hormone in the treatment of abnormal lipid metabolism
in patients with pituitary GH adenoma after surgery, especially the study on the change
of liver fat content. The investigators intend to apply a recombinant human growth
hormone dose of 1 mg/week (6 IU is 1 mg) to GH adenoma patients with GHD and NAFLD after
GH adenoma surgery, aiming to increase the insulin-like growth factor-1 of patients to
the median of the normal level of peers, with a treatment duration of 24 weeks. After
treatment, changes in liver fat content at baseline and 24 weeks after intervention will
be measured by proton magnetic resonance spectroscopy (1H MRS) and Fibroscan liver
stiffness. The changes in metabolic parameters (body weight, body mass index (BMI), waist
circumference, fasting blood glucose, blood lipids, high iron content, and other
metabolic-related inflammatory factors) before and after recombinant human growth hormone
treatment will be evaluated.
This study aims to evaluate the efficacy and safety of recombinant human growth hormone
in the treatment of GHD-induced NAFLD patients with abnormal lipid metabolism after GH
adenoma surgery and propose a suitable treatment method for people with abnormal lipid
metabolism due to GHD after GH adenoma surgery, providing a direct basis for establishing
a standardized clinical treatment path in the next step.
The Department of Neurosurgery of Zhongshan Hospital Affiliated to Fudan University
carries out more than 300 cases of various types of pituitary tumors every year,
including more than 100 cases of pituitary GH adenoma. It has developed a
multidisciplinary joint clinic for pituitary tumors earlier in China and has rich
experience in the diagnosis and treatment of pituitary tumors, meeting the needs of 40
enrolled cases. The Department of Endocrinology has been committed to the evaluation of
lipid metabolism disorders in nonalcoholic fatty liver for a long time. Currently,
ultrasound and imaging are proficient in non-invasive methods of determining liver fat,
such as MRS liver stiffness test. As a large Class III hospital in Shanghai, with a
wealth of pituitary tumor patients, it can meet the enrollment requirements of subjects,
and the endocrinology department can complete the assessment of lipid metabolism
disorder. Detailed exit criteria and rescue plans have been jointly developed. Adverse
events that may occur during the study were defined and addressed in detail.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
- Have fully understood the informed consent and signed the informed consent;
- Age: 18-60 years old;
- Patients diagnosed with adult growth hormone deficiency (AGHD) (GH stimulation test:
GH peak ≤5ug/l or organic hypothalamic-pituitary disease ≥3 pituitary hormone
deficiency with IGF-1 < -2SD)
- Patients with pituitary growth hormone adenoma proved pathologically after surgery
- Anterior pituitary hormone supplementation (except growth hormone)
- The liver fat content was more than 11% after six months to two years of operation
by proton magnetic resonance spectroscopy (1H MRS).
- Those who have not taken lipid-regulating drugs (statins, Bates);
- Blood pressure <150/95mmHg, did not take any antihypertensive drugs;
Exclusion Criteria:
- Have any of the following liver disease history: chronic hepatitis, cirrhosis, liver
cancer, autoimmune liver disease, alcoholic liver disease, hereditary liver disease
- Significant abnormal liver function: ALT or AST≥ 2 times the upper limit of normal;
HBsAg (+), and/or HCV-Ab (+);
- Patients with serum creatinine value ≥1.5mg/dL (133umol/L);
- Patients with severe heart disease (patients with a history of myocardial infarction
and heart failure and/or severe arrhythmia);
- Patients with severe infection, other operations within 6 months, or severe trauma;
- Alcohol consumption (alcohol): male ≥140g/week; Female ≥70g/week;
- Poorly controlled diabetic patients: HbA1c >9.5% within three months; Or use
hypoglycemic drugs that may affect liver histopathology, including pioglitazone,
GLP-1, and DP-4 inhibitors;
- Patients with allergy or intolerance to the same drug used in the trial;
- In the next 1 year, there are pregnancy plans or breastfeeding patients or patients
with mental disorders;
- Patients who have participated in other clinical trials within 24 weeks.
Gender:
All
Minimum age:
18 Years
Maximum age:
60 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
Shanghai Zhongshan Hospital
Address:
City:
Shanghai
Zip:
200032
Country:
China
Status:
Recruiting
Contact:
Last name:
Tao Xie, doctorate
Phone:
13524281211
Email:
xie.tao@zs-hospital.sh.cn
Start date:
January 1, 2023
Completion date:
December 31, 2025
Lead sponsor:
Agency:
Shanghai Zhongshan Hospital
Agency class:
Other
Source:
Shanghai Zhongshan Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06448195
