Growth Hormone Replacement for Gulf War Illness

(GWIT Trial)

Recruiting at 1 trial location

Overseen By Audri Villalon

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Baylor College of Medicine

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

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

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Approved in 3 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 15

Duration: 6 months

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether growth hormone therapy (recombinant human growth hormone) can aid veterans with Gulf War Illness (GWI) who also have a growth hormone deficiency. The primary goal is to determine if it reduces trunk fat and improves GWI symptoms. Veterans who served in Operation Desert Storm or Desert Shield and have been diagnosed with both GWI and growth hormone deficiency are suitable candidates for this study. Participants will undergo growth hormone therapy for six months, with several check-ups to monitor changes in body composition and symptoms. The study aims to determine if a larger trial should be conducted in the future. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering veterans a chance to contribute to potentially groundbreaking 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.

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

Research has shown that human growth hormone treatments are usually safe. In one past study, some participants experienced side effects, but these were mostly mild. Common side effects included joint pain, swelling, and muscle aches, which most found manageable. The FDA has already approved this treatment for other uses, indicating its well-known safety. While this can be reassuring, monitoring for any new or unusual symptoms during the trial remains important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for Gulf War Illness, which often focus on managing symptoms with medications like pain relievers and antidepressants, growth hormone replacement therapy (GHRT) targets the underlying hormonal imbalance. GHRT uses recombinant human growth hormone to potentially improve body composition by reducing truncal fat mass. Researchers are excited about its ability to directly influence the body's metabolism and overall function, offering a novel approach to addressing the root causes of symptoms rather than just alleviating them. This approach could provide a more comprehensive improvement in patients’ quality of life.

What evidence suggests that growth hormone replacement therapy might be an effective treatment for Gulf War Illness?

Research shows that recombinant human growth hormone (rhGH), a treatment participants in this trial may receive, might help treat Gulf War Illness (GWI) by enhancing body health and brain function. Studies have found that veterans with GWI often lack sufficient growth hormone as adults, leading to increased belly fat and cognitive issues. Early results suggest that rhGH treatment can reduce belly fat by about 5.3%. Some research also indicates it might improve learning and memory. These findings offer hope that rhGH could be a useful treatment for veterans with GWI. ^{1 2 4 5 6}

Who Is on the Research Team?

Ricardo Jorge, MD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

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.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Recombinant human growth hormone

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.

How Is the Trial Designed?

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 United States, European Union, Canada for the following indications:

Approved in United States as Somatotropin for:

• Adult growth hormone deficiency
• Pediatric growth hormone deficiency
• Prader-Willi syndrome
• Turner syndrome
• Short stature homeobox-containing gene (SHOX) deficiency
• Chronic kidney disease

Approved in European Union as Somatotropin for:

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

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+

United States Department of Defense

Collaborator

Trials

940

Recruited

339,000+

Published Research Related to This Trial

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]

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 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]

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 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]

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrial.be clinicaltrial.be/en/details/17299?per_page=20&recruiting=1&enrolling_by_invitation=1&active_not_recruiting=1&not_yet_recruiting=0&completed=0&only_recruiting=0&only_eligible=0

Growth Hormone Replacement in Veterans With GWI and ... The objective of this research is to conduct a clinical trial to determine whether GHRT can improve body composition, cognitive function, sleep ...

2. apps.dtic.mil apps.dtic.mil/sti/trecms/pdf/AD1221161.pdf

Growth Hormone Replacement Therapy in Veterans with Gulf ... The primary hypothesis is that participants receiving rhGH for 6-months will show improvements in body composition (i.e., truncal fat mass ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S002432052300543X

Hormonal changes in veterans with Gulf War Illness The frequency of AGHD was significantly higher in veterans with GWI compared to controls. Recombinant human growth hormone replacement therapy ( ...

4. apps.dtic.mil apps.dtic.mil/sti/trecms/pdf/AD1191317.pdf

Growth Hormone Replacement Therapy in Veterans with Gulf ... The primary hypothesis is that participants receiving rhGH for. 6-months will show improvements in body composition (i.e., truncal fat mass reduction of 5.3% or ...

5. mdpi.com mdpi.com/1422-0067/26/17/8516

Evaluation of the Therapeutic Potential of Synthetic Growth ... Our findings suggest that the MIA-690 dosage is sufficient to improve learning deficits in experimental GWI exposures. Keywords: Gulf War illness; ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05355272/growth-hormone-replacement-in-veterans-with-gwi-and-aghd-gwit

Growth Hormone Replacement in Veterans With GWI and ... The goal of the GWIT Study is to assess whether growth hormone replacement therapy is a safe and effective treatment for veterans with Gulf War Illness (GWI)