Clinical trial NCT06354023: Human Growth Hormone Injections in the Knee Joint to Treat Osteoarthritis
Official title: Administration of Recombinant Human Growth Hormone in the Knee Joint of Patients Suffering from Osteoarthritis
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
Conditions: Osteoarthritis, Knee
Keywords: Intra-Articular Injection
Somatropin
Growth Hormone
Lead sponsor: BioShift Life Sciences
Sponsor class: OTHER
First posted: 2024-04-09
Enrollment: 23
Sex: ALL
Minimum age (years): 18
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: The proposed clinical trial is a single-arm intervention model. Once per week for six weeks, each participant will receive an intra-articular injection of recombinant human growth hormone (rGH) 15 IU in their affected knee. During the treatment course, the participants will use the same knee brace and crutches (as needed) and be given the same exercises to complete at home. They will all be evaluated 8 weeks, 6 months, and 12 months after their initial injection.
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to learn if growth hormone injections can be used to treat osteoarthritis (OA) in the knee. Human studies have shown that repeated injections of human growth hormone leads to the production of articular chondrocytes, which are the cells that make up the cartilage in the knee joint. Restoring cartilage in the knee can alleviate pain, improve function, and postpone the need for a joint replacement procedure. The main questions the study aims to answer are:

* Do growth hormone injections in the knee joint stimulate cartilage growth?
* Do the injections lower pain and stiffness in the participant's treated knee?
* Does the participant have more mobility after the injections?

The physician will monitor the participant's progress through X-ray images, questionnaires, and physical evaluation of the treated knee.

For the trial, participants will:

* Receive a growth hormone injection in their knee once per week for six weeks, for a total of 6 injections.
* Complete at-home exercises during the treatment period.
* Use crutches as needed during the trial.
* Have X-rays taken at 8 weeks, 6 months, and 12 months after the first injection.
* Go to follow-up visits at 8 weeks, 6 months, and 12 months after the first injection.
* Complete treatment surveys before treatment starts and after it is finished.

Detailed description: The trial and protocol are being reviewed by PearlIRB, an institutional review board, at 29 East McCarty St, Suite #100, Indianapolis, IN 46225.

Clinical and non-clinical studies of repeated intra-articular human growth hormone injections have shown to regrow cartilage and reduce symptoms of osteoarthritis (OA). Recently, a population of stem cells, osteochondroreticular (OCR) stem cells, were identified in adult mice. OCR stem cells were found to display growth hormone (GH) receptors and can undergo asymmetric division. The cells respond to GH in a paracrine-like manner with insulin-like growth factor 1 (IGF-1) and have been found to differentiate into chondrocytes on the articular surfaces of mice. Chondrocytes have been shown to have few if any, GH receptors, so it is likely that the OCR cells are the target of GH and are responsible for the treatment effect. It is hypothesized that the weekly injections of recombinant human growth hormone (rGH) into the knee joint of patients suffering from OA will act upon chondrocyte progenitor cells to divide and release IGF-1 that will act in a paracrine manner and promote the formation of new hyaline cartilage in the joint capsule.

People with OA will be recruited through the participating physicians, friends, and family of the clinic, and word of mouth. Participants will be identified based on physician assessment of the inclusion and exclusion criteria. After discussing the purpose of the study, if the patient wishes to participate, they will read and sign the informed consent form, acknowledging they understand the trial they are participating in. The participants will undergo a blood draw to ensure they meet the inclusion criteria in the study. When the participant's blood work has been completed and if the levels fall within the ranges of the study, the patient will have preliminary X-ray images taken of their affected knee.

The participant's knee will be assessed by a physician using the Knee Society Score and the Kellgren-Lawrence grading scale. The participant and physician complete the Knee Society Score form. The questionnaire is scored out of 100 possible points; the higher the score, the less severe a patient's OA. The Kellgren-Lawrence scale is a 0 (no signs of OA) to 4 (severe OA) grading system that uses radiographs of the knee to evaluate the severity of OA. Due to low intra- and interobserver reliability, automated imaging software will be used to analyze changes in each participant's radiographs.

The treatment plan for each participant will involve a weekly intra-articular injection of 15IU rGH with Lidocaine and Marcaine for a duration of 6 weeks. Participants will have crutches and be weight-bearing as tolerated during the treatment. To monitor the progress, X-ray images of the treated knee will be taken before the first injection, 8 weeks after the initial injection, and at 6 and 12 months after the initial injection. Additional blood draws will be conducted immediately before the 6th injection and in the afternoon after the 6th injection to evaluate circulating IGF-1 levels. The physician will assess the injected knee using the Knee Society Score and the Kellgren-Lawrence grading scale before treatment begins and at 8 weeks, 6 months, and 12 months after the initial injection.

The study will have 23 subjects, and we hope that this is enough to allow us to reject our null hypothesis. The trial is constrained to some degree by the cost of the growth hormone.

The source documents will be the Knee Society Score questionnaire and the Kellgren-Lawrence grade that will be determined by automated radiographic classifiers. The two tests will be evaluated using a one-tailed t-test to determine significance between the different time periods with a p-value \< 0.05.

Patient safety data will be presented as a combination of patient-reported safety, physician-reported patient safety, and any adverse events (AE) or serious adverse events (SAE) as reported by the physicians. All AE and SAE will be collected and submitted to the PI at the time of their identification. All submissions will be acknowledged within 24 hours. All submissions will have an association determination within 72 hours by Dr. John Sledge. Any life-threatening event that is determined to be related or possibly related to the study will be seen as potential grounds for study termination. Any Unanticipated Problem will be seen as potential grounds for study termination.

Eligibility criteria: Inclusion Criteria:

* Should be between 18-72 years old
* Can comply with partial weight-bearing status during the study
* Should have symptomatic knee arthritis

  * Knee pain ≥3 months
  * Kellgren-Lawrence score between 1-3
* Should have complete blood count levels within healthy ranges
* Should have complete renal function based on the metabolic panel
* Should have IGF-1 levels within the designated healthy range for their age
* Should have normal thyroid function

Exclusion Criteria:

* Should not have a current or previous cancer diagnosis
* Should not have rheumatoid arthritis
* Should not have hemophilia
* Should not abnormal knee alignment or stability
* Should not be pregnant or trying to get pregnant
* Should not have had a knee injection within the last 3 months
* Should not have a history of drug or alcohol abuse
* Should not have a diabetes diagnosis
* Should not have inflammatory or septic knee arthritis
* Should not have any signs of infection
* Should not have used anti-coagulants and/or NSAIDs 7 days before treatment begins

Primary outcomes:
measure: Knee Society Score
timeFrame: The questionnaire will be filled out at 4 time points: before treatment begins and at 8 weeks, 6 months, and 12 months after the first injection.
measure: Kellgren-Lawrence Grading Scale
timeFrame: The grade will be assigned at 4 time points: before treatment begins and at 8 weeks, 6 months, and 12 months after the first injection.
Secondary outcomes:
measure: Serum IGF-1 Levels
timeFrame: The grade will be assigned at 3 time points: before the first injection, immediately before the 6th injection, and one hour after the 6th injection.
Other outcomes:
Locations:
city: Santa Monica
country: United States
facility: BioShift Life Sciences
state: California
Study officials:
affiliation: BioShift Life Sciences
name: John Sledge, MD
role: PRINCIPAL_INVESTIGATOR
References:
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