Growth Hormone Replacement for Gulf War Illness

(GWIT Trial)

Recruiting at1 trial location

Overseen by Ricardo Jorge, MD

Age: 18 - 65

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Baylor College of Medicine

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

Disqualifiers: Psychiatric, Neurologic, Cancer, Substance use, others

No Placebo Group

Prior Safety Data

Approved in 3 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing if giving synthetic growth hormone to veterans with Gulf War Illness and growth hormone deficiency can reduce body fat and improve their symptoms. The study will check if this treatment is safe and effective over several months. If successful, it could lead to better care for these veterans. Growth hormone (GH) treatment has been shown to increase height velocity in children with Prader-Willi syndrome, decrease weight-for-height index values and body fat mass, and have a positive effect on lean body mass during therapy.

Will I have to stop taking my current medications?

The trial requires that participants have been stable on any psychotropic medications for 4 weeks and on all hormone treatments for 3 months. You cannot use growth hormone, estrogen, hormonal contraceptives, progestin, insulin growth factor 1, or chronic glucocorticoids in high doses during the trial.

What data supports the effectiveness of the drug recombinant human growth hormone (rhGH) for treating Gulf War Illness?

Research shows that recombinant human growth hormone (rhGH) can improve metabolism, body composition, and physical and psychological function in adults with growth hormone deficiency. This suggests it might help with similar symptoms in Gulf War Illness. ^{1 2 3 4 5}

Is recombinant human growth hormone (rhGH) generally safe for humans?

Recombinant human growth hormone (rhGH) is generally considered safe when used at replacement doses, with large studies showing a favorable safety profile. However, high doses may cause DNA damage in cells, and there have been reports of increased mortality risk, although these findings are not consistent across all studies. ^{6 7 8 9 10}

How is the drug recombinant human growth hormone (rhGH) unique in treating Gulf War Illness?

Recombinant human growth hormone (rhGH) is unique for Gulf War Illness as it is not a standard treatment for this condition, and it works by potentially improving metabolism, body composition, and quality of life, which are areas often affected in this illness. ^{4 9 11 12 13}

Research Team

Ricardo Jorge, MD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

This trial is for Gulf War veterans under 65 with Gulf War Illness and Adult Growth Hormone Deficiency, who are stable on current medications. They must not be pregnant, in other drug trials without approval, have certain psychiatric or neurological disorders, recent illicit drug use (except cannabis), extreme obesity, or a history of growth hormone issues due to other causes.

Inclusion Criteria

I am 64 years old or younger.

I have been on the same hormone treatment for at least 3 months.

Able and willing to provide informed consent to participate in the study and complete the study protocol

Exclusion Criteria

I am allergic to growth hormone or its ingredients.

I have a psychiatric condition that significantly affects my daily life.

I have a neurological condition that significantly affects my daily life, excluding traumatic brain injury.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Treatment

Participants receive recombinant human growth hormone for 6 months with biweekly titration for 6 weeks

6 months

In-clinic follow-up visits at Days 14, 40, 65, 90, and 180

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Placebo (Drug)
• Recombinant human growth hormone (Hormone Therapy)

Trial Overview The study tests if Growth Hormone Replacement Therapy (GHRT) over six months can reduce belly fat in these veterans compared to a placebo. It's a double-blind trial meaning neither the participants nor the researchers know who gets GHRT or placebo until after the results are collected.

Participant Groups

Group I: Growth Hormone Replacement Therapy Experimental Treatment 1 Intervention

Patients will be started at a dose of 200-300 mcg/d of daily injections of GHRT. A biweekly titration period of 6 weeks will be performed in increments of 100 mcg/d as needed until IGF-1 levels are between +1 and +2 standard deviation score, up to a maximum dose of 2,000 mcg/d, provided the dose is well tolerated. The duration of the intervention is 6-months. Participants will complete in-clinic follow-up visits at Days 14, 40, 65, 90, and 180. The primary outcome will be the change in truncal fat mass percentage from baseline to six months measured by dual-energy x-ray absorptiometry (DEXA).

Recombinant human growth hormone is already approved in Canada for the following indications:

Approved in Canada as Somatotropin for:

• Growth hormone deficiency in children and adolescents
• Growth hormone deficiency in adults
• Prader-Willi syndrome
• Turner syndrome

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

Paul Klotman

Baylor College of Medicine

Chief Executive Officer since 2010

MD, PhD

James Versalovic

Baylor College of Medicine

Chief Medical Officer since 2020

MD from Baylor College of Medicine

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Pete Hegseth

United States Department of Defense

Chief Executive Officer

Bachelor's degree in Political Science from Princeton University, JD from Harvard Law School

Lisa Hershman

United States Department of Defense

Chief Medical Officer since 2021

MD from Uniformed Services University of the Health Sciences

Findings from Research

Recombinant human growth hormone (rhGH) significantly promotes growth in children with growth hormone deficiency (GHD), leading to increases in body height and growth velocity across different pituitary developmental conditions, as shown in a study of 90 children.

The treatment was found to be safe, with no significant differences in adverse reactions among children with pituitary dysplasia, normal pituitary, or enlarged pituitary growth, indicating that rhGH is an effective and safe option for enhancing growth in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic effect of recombinant human growth hormone on children with growth hormone deficiency and different pituitary developmental conditions: a prospective study]. Wei, XF., Zhang, YY., Yan, ZP., et al.[2023]

In a study involving 585 children with growth hormone deficiency, biweekly PEGylated rhGH therapy showed a height velocity that was comparable to weekly and daily rhGH treatments, but it did not meet the non-inferiority threshold for height SD scores, indicating it may not be as effective as the other regimens.

Safety profiles were similar across all treatment groups, with no significant differences in adverse events or levels of IGF-2 and IGFBP-2, suggesting that biweekly PEG-rhGH is safe but may not be the best option for maximizing growth outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted Trial. Sun, C., Lu, B., Liu, Y., et al.[2022]

In a study of 22 stroke patients, those receiving recombinant human growth hormone (rhGH) alongside rehabilitative therapy showed significant improvement in functional recovery, as measured by the Korean Modified Barthel Index (K-MBI), compared to the control group.

The rhGH group reported no fatigue during the study period and exhibited less decline in neural fiber integrity, suggesting potential benefits in both physical recovery and overall well-being without any harmful side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of recombinant human growth hormone therapy in patients with completed stroke: a pilot trial. Song, J., Park, K., Lee, H., et al.[2021]

Synthetic recombinant human growth hormone (GH) has enhanced our understanding of GH's effects on metabolism and health, particularly in adults with GH deficiency, which can lead to significant health issues.

GH replacement therapy at lower doses for adults can effectively reverse many health abnormalities associated with GH deficiency, and when dosed correctly, it has few adverse effects and does not appear to increase cancer or cardiovascular risks based on current studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diagnosis and treatment of growth hormone deficiency in adults. Kargi, AY., Merriam, GR.[2021]

Children with hypopituitarism treated with recombinant human growth hormone (rGH) have significantly better adult height outcomes compared to those treated with pituitary-derived human growth hormone (pGH), with current heights ranging from -1.5 to -0.7 height standard deviations from control populations.

The treatment with rGH has not adversely affected bone maturation or puberty onset, and while higher doses during puberty have shown positive effects, standard dosing is likely to continue due to financial and safety considerations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Growth hormone therapy in childhood-onset growth hormone deficiency: adult anthropometric and psychological outcomes. Sandberg, DE., MacGillivray, MH.[2022]

A pilot study involving 18 healthy women showed that short-term treatment with supra-physiological doses of recombinant human growth hormone (rhGH) for 3 weeks led to a temporary increase in DNA damage in lymphocytes, indicating potential risks associated with high doses of rhGH.

Despite the increase in IGF-I levels during treatment, the study found no lasting changes in IGF-I or IGFBP-3 levels 30 days after stopping rhGH, suggesting that while there may be immediate effects on DNA integrity, these do not persist long-term.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Short-term, supra-physiological rhGH administration induces transient DNA damage in peripheral lymphocytes of healthy women. Fantini, C., Sgrò, P., Pittaluga, M., et al.[2018]

Recombinant human growth hormone (rGH) is effective for treating various growth disorders, providing a reliable treatment option for conditions like Turner syndrome and idiopathic short stature.

Recent studies, including the National Cooperative Growth Study and the EU SAGhE study, indicate that rGH has a favorable safety profile, which is important for physicians when considering treatment options for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Growth Hormone and Treatment Controversy; Long Term Safety of rGH. Divall, SA., Radovick, S.[2021]

In patients with Prader Willi Syndrome, treatment with recombinant human growth hormone (rhGH) does not affect hypogonadism but may improve cognitive function.

For patients with Idiopathic Short Stature, rhGH treatment can increase near adult height by 3-4 cm, and certain characteristics can help identify those who will respond best to the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recent updates on recombinant human growth hormone outcomes and adverse events. Watson, SE., Rogol, AD.[2022]

In a study of 24 male patients with adult growth hormone deficiency (AGHD) due to multiple pituitary hormone deficiency (MPHD), stopping recombinant human growth hormone (rhGH) therapy after linear growth completion led to significant increases in body fat and obesity rates, with 29.2% of participants classified as obese.

The AGHD group also experienced a notable increase in waist circumference and a decrease in fat-free mass, indicating adverse changes in body composition, while their blood pressure was lower and they showed significant hyperuricemia compared to age-matched controls.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Body composition and metabolic health of young male adults with childhood-onset multiple pituitary hormone deficiency after cessation of growth hormone treatment. Yang, H., Wang, L., Qiu, X., et al.[2021]

Recombinant human growth hormone (rhGH) has a strong safety profile, supported by extensive studies involving over 600,000 patient-years of exposure, indicating it is generally safe for children receiving this therapy.

While there have been reports of increased mortality risk associated with growth hormone therapy, these risks appear to be linked to factors like small size at birth, and further long-term safety studies are needed, especially with new long-acting growth hormone products.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Monitoring rhGH Safety: rhGH Registries, SAGhE and Future Needs. Miller, BS., Rosenfeld, RG.[2019]

In a cohort study of 64 adult patients who discontinued recombinant human growth hormone (rhGH) replacement for over 12 months, significant metabolic changes were observed, particularly in those under 60 years, including an increase in body fat percentage and a decrease in femoral neck bone density.

The study found that while glucose and cholesterol levels remained stable, younger patients experienced a rise in HDL cholesterol and a slight increase in the percentage of those on statins, indicating potential shifts in lipid profiles after stopping rhGH therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of discontinuation of growth hormone replacement in adult GH-deficient patients: a cohort study and a systematic review of the literature. Appelman-Dijkstra, NM., Rijndorp, M., Biermasz, NR., et al.[2018]

In a study of 283 patients with adult growth hormone deficiency due to nonfunctioning pituitary adenoma or craniopharyngioma, rhGH treatment was associated with a lower recurrence rate of pituitary tumors (19.5% in treated patients vs. 29.7% in controls).

However, after adjusting for other factors, rhGH treatment did not significantly affect the risk of tumor recurrence, indicating that it has a neutral effect on pituitary tumor recurrence in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Growth Hormone Therapy Does Not Increase the Risk of Craniopharyngioma and Nonfunctioning Pituitary Adenoma Recurrence. Losa, M., Castellino, L., Pagnano, A., et al.[2021]

In a study of 55 pediatric patients with growth hormone deficiency (GHD) receiving recombinant human growth hormone (rhGH) therapy for 6-24 months, no patients experienced dangerously low levels of free thyroxine (FT4), indicating safety in thyroid function during treatment.

However, the study found that FT4 levels decreased significantly over time, particularly in the puberty group by the 12th month, suggesting that rhGH therapy may influence thyroid hormone metabolism, necessitating regular monitoring of thyroid function in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of recombinant human growth hormone therapy on thyroid function in pediatric patients with growth hormone deficiency. Yao, Q., Zheng, D., Liang, Y., et al.[2022]

References

1. China pubmed.ncbi.nlm.nih.gov

[Therapeutic effect of recombinant human growth hormone on children with growth hormone deficiency and different pituitary developmental conditions: a prospective study]. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Reduced Effectiveness and Comparable Safety in Biweekly vs. Weekly PEGylated Recombinant Human Growth Hormone for Children With Growth Hormone Deficiency: A Phase IV Non-Inferiority Threshold Targeted Trial. [2022]

3. Korea (South) pubmed.ncbi.nlm.nih.gov

The effect of recombinant human growth hormone therapy in patients with completed stroke: a pilot trial. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Diagnosis and treatment of growth hormone deficiency in adults. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Growth hormone therapy in childhood-onset growth hormone deficiency: adult anthropometric and psychological outcomes. [2022]

6. Italy pubmed.ncbi.nlm.nih.gov

Short-term, supra-physiological rhGH administration induces transient DNA damage in peripheral lymphocytes of healthy women. [2018]

7. Germany pubmed.ncbi.nlm.nih.gov

Growth Hormone and Treatment Controversy; Long Term Safety of rGH. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Recent updates on recombinant human growth hormone outcomes and adverse events. [2022]

9. Germany pubmed.ncbi.nlm.nih.gov

Body composition and metabolic health of young male adults with childhood-onset multiple pituitary hormone deficiency after cessation of growth hormone treatment. [2021]

10. Israel pubmed.ncbi.nlm.nih.gov

Monitoring rhGH Safety: rhGH Registries, SAGhE and Future Needs. [2019]

11. England pubmed.ncbi.nlm.nih.gov

Effects of discontinuation of growth hormone replacement in adult GH-deficient patients: a cohort study and a systematic review of the literature. [2018]

12. United States pubmed.ncbi.nlm.nih.gov

Growth Hormone Therapy Does Not Increase the Risk of Craniopharyngioma and Nonfunctioning Pituitary Adenoma Recurrence. [2021]

13. China pubmed.ncbi.nlm.nih.gov

The effects of recombinant human growth hormone therapy on thyroid function in pediatric patients with growth hormone deficiency. [2022]