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

Trial Summary

What is the purpose of this trial?

This trial is testing if giving extra growth hormone can help improve the quality of life for adults who have low growth hormone levels and mild brain injuries. Growth hormone treatment has been shown to improve quality of life in adults with growth hormone deficiency.

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.

What data supports the effectiveness of the drug Somatropin for growth hormone deficiency and concussion?

Research shows that Omnitrope, a form of Somatropin, is effective in treating growth hormone deficiency in both adults and children, improving growth rates and quality of life. Additionally, growth hormone replacement therapy has been shown to improve quality of life in patients with traumatic brain injury, which is related to growth hormone deficiency. ^{1 2 3 4 5}

How is the drug Somatropin unique for treating growth hormone deficiency and concussion?

Somatropin is unique because it is a growth hormone replacement therapy that can improve quality of life in patients with growth hormone deficiency, including those with traumatic brain injury (TBI), a common cause of this deficiency. It is a biosimilar to other growth hormone treatments, meaning it is highly similar to existing options but may offer a more cost-effective alternative. ^{1 2 3 5 6}

Research Team

Jose M. Garcia, MD PhD

Principal Investigator

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

Eligibility Criteria

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

I have a neurological condition, not TBI, affecting my quality of life.

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

References

1. Italy 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. [2018]

2. Scotland pubmed.ncbi.nlm.nih.gov

Metabolic and quality of life effects of growth hormone replacement in patients with TBI and AGHD: A pilot study. [2023]

3. United States 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. [2021]

4. England 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. [2018]

5. Switzerland 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. [2007]

6. Sweden pubmed.ncbi.nlm.nih.gov

Limited Adherence to Growth Hormone Replacement in Patients with Traumatic Brain Injury. [2022]