Somatropin for Growth Hormone Deficiency and Concussion

(GRIT Trial)

Recruiting at 4 trial locations

Overseen By Deane V Walker, MHA BS AB

Age: 18 - 65

Sex: Any

Trial Phase: Phase 3

Sponsor: VA Office of Research and Development

Must not be taking: Growth hormone, Estrogen, Progestin, others

Disqualifiers: Moderate TBI, Schizophrenia, Cancer, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

172 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if growth hormone replacement therapy (GHRT) can enhance the quality of life for individuals with adult growth hormone deficiency and mild traumatic brain injury (mTBI). The treatment under evaluation is Somatropin, a form of human growth hormone, compared to a placebo. Veterans with one or more mild brain injuries from military service and a diagnosis of growth hormone deficiency may be suitable candidates for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, providing participants an opportunity to contribute to potentially groundbreaking treatment advancements.

Will I have to stop taking my current medications?

The trial requires that you have been stable on any psychotropic medications for 4 weeks and on all other hormone treatments for 3 months. You cannot currently use growth hormone, estrogen, progestin, IGF-I, or high doses of glucocorticoids.

Is there any evidence suggesting that Somatropin is likely to be safe for humans?

In a previous study, researchers found that somatropin, a treatment for growth hormone deficiency, can cause some side effects. The most common are swelling from fluid buildup and pain in the joints and muscles. Adjusting the dose usually helps manage these issues. Another study showed that somatropin is generally as safe as other growth hormone treatments, with most patients tolerating it well. While side effects can occur, not everyone experiences them, and they are often manageable with proper care. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for growth hormone deficiency?

Unlike the standard treatments for growth hormone deficiency, which typically include various synthetic hormone therapies, Somatropin is unique because it utilizes recombinant human growth hormone. This means it's designed to mimic the natural growth hormone produced by the body, potentially offering a more natural alternative. Researchers are excited about Somatropin because it not only aims to address growth hormone deficiency but may also have beneficial effects for individuals who've suffered a concussion, offering a dual-purpose treatment option. This could lead to more comprehensive care for patients experiencing these conditions simultaneously.

What evidence suggests that Somatropin might be an effective treatment for growth hormone deficiency and concussion?

Research has shown that somatropin, a type of growth hormone therapy, effectively treats growth hormone deficiency. Studies have found that it improves body composition by increasing muscle and reducing fat in patients with this condition. Patients using somatropin have experienced significant improvements in growth and overall health. For adults with growth hormone deficiency, somatropin has improved quality of life, boosting energy levels and physical health. In this trial, some participants will receive somatropin to evaluate its effectiveness in treating conditions like mild traumatic brain injury (mTBI), which remains under study. Other participants will receive a placebo for comparison. ^{1 5 6 7 8}

Who Is on the Research Team?

Jose M. Garcia, MD PhD

Principal Investigator

VA Puget Sound Health Care System Seattle Division, Seattle, WA

Are You a Good Fit for This Trial?

This trial is for veterans with mild traumatic brain injury (mTBI) and adult growth hormone deficiency (AGHD). Participants must have a diagnosed GH deficiency, experience from combat, stable use of psychotropic medications, and not be using illicit drugs. Pregnant women or those not on contraception are excluded.

Inclusion Criteria

One or more mTBI sustained during military service at least 12 months prior to the screening date, as noted via the CRAFT survey

OEF/OIF/OND Veteran

Score of 1 or more on Combat Experiences sub-scale of Deployment Risk and Resilience Inventory-2 (DRRI-2)

Exclusion Criteria

I am currently using growth hormone, estrogen supplements, progestin, IGF-I, or high-dose glucocorticoids.

History of moderate or severe TBI

History of bipolar disorder, schizophrenia, or other concurrent psychotic disorder

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive recombinant human Growth Hormone or placebo daily for 6 months

6 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Somatropin

Trial Overview The study aims to see if growth hormone replacement therapy (GHRT) with Somatropin improves quality of life compared to a placebo in patients who have both mTBI and AGHD. It's a controlled test where some get the real treatment and others get an inactive substance.

How Is the Trial Designed?

Group I: Growth Hormone Replacement Therapy Active Control 1 Intervention

Recombinant Human Growth Hormone

Group II: Placebo Placebo Group 1 Intervention

Placebo

Somatropin is already approved in European Union, United States, Canada, Japan, Switzerland for the following indications:

Approved in European Union as Genotropin for:

• Growth hormone deficiency
• Turner syndrome
• Chronic kidney disease
• Short stature homeobox-containing gene (SHOX) deficiency
• Small for gestational age (SGA) with no catch-up growth

Approved in United States as Humatrope for:

• Growth hormone deficiency
• Turner syndrome
• Idiopathic short stature
• Short stature associated with Noonan syndrome
• Short stature associated with Turner syndrome in pediatric patients whose epiphyses are closed

Approved in Canada as Norditropin for:

• Growth hormone deficiency
• Turner syndrome
• Chronic kidney disease
• Short stature homeobox-containing gene (SHOX) deficiency
• Small for gestational age (SGA) with no catch-up growth

Approved in Japan as Nutropin for:

• Growth hormone deficiency
• Turner syndrome
• Chronic kidney disease

Approved in Switzerland as Omnitrope for:

• Growth hormone deficiency
• Turner syndrome
• Chronic kidney disease
• Short stature homeobox-containing gene (SHOX) deficiency
• Small for gestational age (SGA) with no catch-up growth

Who Is Running the Clinical Trial?

VA Office of Research and Development

Lead Sponsor

Trials

1,691

Recruited

3,759,000+

Published Research Related to This Trial

Valtropin, a new biosimilar recombinant human growth hormone, demonstrated comparable efficacy to Humatrope in increasing height velocity in children with growth hormone deficiency, with a height velocity of 11.3 cm/year for Valtropin versus 10.5 cm/year for Humatrope over one year.

Both treatments showed similar safety profiles, with no significant differences in adverse events or bone maturation acceleration, indicating that Valtropin is a safe and effective option for treating children with growth hormone deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, double-blind study to assess the efficacy and safety of valtropin, a biosimilar growth hormone, in children with growth hormone deficiency. Peterkova, V., Arslanoglu, I., Bolshova-Zubkovskaya, E., et al.[2007]

The PATRO Adults study is a large, long-term observational study designed to assess the safety and efficacy of somatropin (Omnitrope(®)) in adults with growth hormone deficiency, involving multiple centers across Europe.

This study will provide valuable insights into the long-term effects of Omnitrope(®) on various health factors, including diabetes development, tumor recurrence, and overall quality of life, while monitoring adverse events and safety outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rationale and design of PATRO Adults, a multicentre, noninterventional study of the long-term efficacy and safety of Omnitrope(®) for the treatment of adult patients with growth hormone deficiency. Beck-Peccoz, P., Minuto, F., Leal-Cerro, A., et al.[2021]

In a study of 52 patients, only 52% of those with traumatic brain injury adhered to human growth hormone therapy after one year, compared to 86% adherence in patients with non-traumatic brain injury.

The lower adherence in traumatic brain injury patients may be influenced by cognitive and psychosocial challenges, suggesting that these factors should be considered when evaluating treatment benefits.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Limited Adherence to Growth Hormone Replacement in Patients with Traumatic Brain Injury. Lithgow, K., Debert, CT., Kline, GA.[2022]

In a study of 67 Italian patients with growth hormone deficiency, Omnitrope® was found to be effective in improving health markers like insulin-like growth factor-1 levels and body composition over an average treatment duration of 45.4 months.

While 55.2% of patients experienced adverse events, none were deemed related to Omnitrope®, indicating that it is generally safe for long-term use in adults with growth hormone deficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of Omnitrope® in adults with growth hormone deficiency: Italian interim analysis of the PATRO Adults study. Ferone, D., Profka, E., Gasco, V., et al.[2018]

In a 6-month pilot study involving 7 combat Veterans with traumatic brain injury (TBI) and adult growth hormone deficiency (AGHD), growth hormone replacement therapy (GHRT) was found to be feasible and well-tolerated, with a 71% completion rate and high adherence to daily injections.

While overall quality of life improvements were not statistically significant, GHRT led to notable enhancements in physical strength, cognitive function, and reductions in PTSD symptoms, indicating potential benefits that warrant further investigation in larger studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Metabolic and quality of life effects of growth hormone replacement in patients with TBI and AGHD: A pilot study. Herodes, M., Le, N., Anderson, LJ., et al.[2023]

In a study involving 186 children with various growth disturbances, Omnitrope® was found to be well tolerated, with 35.6% of patients reporting adverse events, mostly mild, such as headaches and abdominal pain.

The treatment with Omnitrope® led to significant improvements in height standard deviation scores (HSDS) and height velocity standard deviation scores (HVSDS), indicating its effectiveness in promoting growth in children, consistent with previous clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term safety and efficacy of Omnitrope®, a somatropin biosimilar, in children requiring growth hormone treatment: Italian interim analysis of the PATRO Children study. Iughetti, L., Tornese, G., Street, ME., et al.[2018]

Citations

1. ncbi.nlm.nih.gov ncbi.nlm.nih.gov/books/NBK596750/

Somatropin for Growth Hormone Deficiency - NCBI Bookshelf There are some concerns regarding long-term outcomes of GH treatment related to an increase in insulin resistance and an increased risk of cancer. It remains to ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3262362/

Somatotropin in the treatment of growth hormone deficiency ... This paper reviews two of the longest standing FDA-approved indications for GH treatment, GH deficiency and Turner syndrome.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT00630487?tab=table

Efficacy of Somatropin in Adult Patients With Isolated ... The study will investigate the effect on growth hormone replacement in patients with isolated growth hormone deficiency on body composition, especially visceral ...

4. novomedlink.com novomedlink.com/growth-related-disorders/products/treatments/norditropin/efficacy-safety/growth-hormone-deficiency.html

Norditropin® Efficacy & Safety: Growth Hormone Deficiency Adjusted mean increases in HSDS over the 2-year period were 0.81, 1.57, and 1.73 in the 0.025, 0.05, and 0.1 mg/kg/day dose groups, respectively1 ...

5. academic.oup.com academic.oup.com/jcem/article/107/7/e2717/6566444

Efficacy and Safety of Weekly Somatrogon vs Daily ... Somatrogon is a long-acting recombinant human growth hormone (rhGH) in development for once-weekly treatment of children with growth hormone deficiency (GHD).

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35405011/

Efficacy and Safety of Weekly Somatrogon vs Daily ... The efficacy of once-weekly somatrogon was noninferior to once-daily somatropin, with similar safety and tolerability profiles.

7. sciencedirect.com sciencedirect.com/science/article/pii/S1043661823001615

Efficacy, safety, quality of life, adherence and cost ... We evaluated the efficacy, safety, adherence, quality of life (QoL) and cost-effectiveness of long-acting growth hormone (LAGH) vs daily growth hormone (GH) ...

8. academic.oup.com academic.oup.com/jcem/article/107/12/3287/6697043

Safety and Efficacy of Pediatric Growth Hormone Therapy A total of 23 163 AEs was reported for 14.4% of patients; 3108 AEs were assessed by the investigators as potentially treatment related for 3.1% of patients.