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Growth Hormone Replacement in Veterans With GWI and AGHD (GWIT) (GWIT)

Primary Purpose

Gulf War Syndrome, Adult Growth Hormone Deficiency

Status

Not yet recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Recombinant human growth hormone

Placebo

About this trial

This is an interventional treatment trial for Gulf War Syndrome focused on measuring recombinant human growth hormone, growth hormone replacement therapy

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Being a veteran of the Gulf War conflict with a history of deployment to Operation Desert Storm or Desert Shield between 1990-91
age less than or equal to 64 years old
have a diagnosis of Gulf War Illness assessed by study investigators
have adult growth hormone deficiency diagnosed by glucagon stimulation test (cut point 3.0 mcg/L if BMI is less than or equal to 25 or 1.0 mcg/L if BMI is greater than 25)
4-week stability on any psychotropic medications
3-month stability on all hormone treatments
able and willing to provide informed consent to participant in the study and complete study protocol

Exclusion Criteria:

history of a psychiatric disorder with substantial impact on functional status or quality of life (e.g., schizophrenia, schizoaffective disorder, bipolar, or other psychotic disorder)
history of neurologic disorder other than traumatic brain injury with substantial impact on the quality of life
other known cause for growth hormone deficiency (GHD) including history of childhood onset GHD, hypothalamic/pituitary disease, history of brain radiation, or genetic mutations known to lead to GHD
active suicidal ideation as determined by a score of 2 points or higher on the Columbia Suicide Severity Rating Scale
suicidal behavior in the past 6 months
contraindication to recombinant human growth hormone (rhGH) such as hypersensitivity to rhGH or any of the components of the supplied product
acute medical illness, active infection, cancer, or decompensated chronic medical illness (e.g., decompensated diabetes mellitus, congestive heart failure, chronic obstructive pulmonary disease)
evidence of substance use disorder in the past 6 months other than mild alcohol or cannabis use disorder diagnosed by clinician at time of screening.
urine toxicology evidence of illicit drug use (excluding cannabis) within the past 90 days prior to screening
BMI > 35 or body weight > 350 lbs
abnormal pituitary anatomy documented by an MRI using a Sella protocol
women who are pregnant or of child-bearing potential who are unable/unwilling to use one of the following barrier contraceptives: condoms, diaphragm, cervical cap, or intrauterine device
current use of the following: growth hormone, estrogen or estrogen-like dietary supplements, hormonal contraceptives, progestin, insulin growth factor 1 (IGF-1), or chronic glucocorticoid use in supraphysiologic doses

15) currently enrolled in any other interventional drug trials unless prior approval is provided by the study chairs and the study sponsor

Sites / Locations

Michael E. DeBakey VA Medical Center
VA Puget Sound Healthcare System

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Growth Hormone Replacement Therapy

Placebo

Arm Description

Drug: Somatropin After randomization 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. Participants will be randomized in a 1:1 ratio to rhGH versus placebo for six months, stratified by participating site. Study participants and study team will be blinded to treatment assignment. 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).

Drug: Placebo After randomization 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. Participants will be randomized in a 1:1 ratio to rhGH versus placebo for six months, stratified by participating site. Study participants and study team will be blinded to treatment assignment. 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).

Outcomes

Primary Outcome Measures

Change in truncal fat mass from baseline to six months

The primary outcome measure is the between-group mean difference of truncal fat mass percentage from baseline to six months. Truncal fat mass will be assessed at baseline, 3-months, and 6-months using calibrated dual energy x-ray absorptiometry (DEXA). A large mean difference corresponds with greater changes in truncal fat mass. Decreased truncal fat mass is associated with reduced risk of cardiovascular disease.

Secondary Outcome Measures

Cardiometabolic Risk Factors

Change in cardiometabolic risk factors from baseline to 6 months measured by fasting low density lipoproteins (LDL) and highly sensitive C-reactive protein levels. A decrease in lipoprotein corresponds with increased lipoprotein metabolism, and lower C-reactive protein levels corresponds with less inflammation. A reduction in both suggests lower risk of cardiometabolic disease.

Lean body mass

The change in appendicular lean body mass between baseline and 6 months will be assessed using calibrated dual energy x-ray absorptiometry. The difference will capture changes in body composition (fat and muscle) with a higher difference corresponding with greater body composition changes.

Assessment of quality of life

Change in the quality of life from baseline to 6 months will be measured by the Quality of Life questionnaire for Adult Growth Hormone Deficiency. The score ranges from 0 to 25, with a score of 25 representing highest symptomatic burden and lower quality of life. A change in score is positively correlated with the patient's perception of treatment benefit, and a score change of 3.5 points is considered clinically meaningful.

Fatigue

Fatigue will be measured using the Fatigue Severity Scale. The questionnaire minimum score is a 9 and maximum score is 63. Higher scores represent greater fatigue severity.

Depression, Anxiety, and Stress

The Depression, Anxiety, and Stress Scale-21 (DASS-21), a 21-item questionnaire, will be used to assess depression, anxiety, and stress symptoms. The score range is 0 - 126 with a higher score representing greater severity or frequency of negative emotional symptoms.

Pain Intensity and Interference

Pain intensity and interference will be assessed using the Defense and Veterans Pain Rating Scale. The questionnaire contains two sections, one assessing current level of pain and the other evaluating the extent to which pain interferes with biopsychosocial factors such as daily activity, sleep, mood, and stress. The minimum score for each section is 0 and maximum score is 10 where higher scores correspond with more intense pain and greater interference.

Full Information

NCT ID

NCT05355272

First Posted

April 20, 2022

Last Updated

September 13, 2023

Sponsor

Baylor College of Medicine

Collaborators

United States Department of Defense

1. Study Identification

Unique Protocol Identification Number

NCT05355272

Brief Title

Growth Hormone Replacement in Veterans With GWI and AGHD (GWIT)

Acronym

GWIT

Official Title

Growth Hormone Replacement Therapy in Veterans With Gulf War Illness and Adult Growth Hormone Deficiency

Study Type

Interventional

2. Study Status

Record Verification Date

September 2023

Overall Recruitment Status

Not yet recruiting

Study Start Date

December 1, 2023 (Anticipated)

Primary Completion Date

May 2025 (Anticipated)

Study Completion Date

September 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Baylor College of Medicine

Collaborators

United States Department of Defense

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

This is a placebo-controlled, double-blind, parallel, Randomized Controlled Trial of 6 months of Growth Hormone Replacement Therapy (GHRT) vs. placebo in Veterans with a history of Gulf War Illness (GWI) and Adult Growth Hormone Deficiency (AGHD). The investigators hypothesize that GHRT will reduce truncal fat mass percentage measured by DEXA (primary outcome). This could provide those veterans with GWI and AGHD a novel therapeutic option (GHRT). The study will also examine the feasibility and safety of a larger efficacy trial.

Detailed Description

There is significant overlap between the symptoms of adult growth hormone deficiency (AGHD) and those of Gulf War Illness (GWI) such as fatigue, chronic pain, depression, anxiety, and cognitive dysfunction. AGHD is also associated with metabolic changes including increased truncal fat mass, dyslipidemia, and increased cerebrovascular risk which can lead to neuroinflammation, neurodegeneration, and functional decline. Growth hormone replacement therapy (GHRT) reverses body composition and metabolic changes. Studies on civilians with AGHD caused by other conditions such as brain tumors suggest GHRT improves fatigue, chronic pain, mood disturbance, cognitive function, and improves quality of life (QoL). This is a phase II, randomized, double-blind, placebo-controlled, futility trial testing the efficacy and safety of GHRT as a treatment option for patients with a history of AGHD and GWI. The primary outcome is to test the efficacy of GHRT versus placebo to change truncal fat mass percentage measured by dual energy x-ray absorptiometry (DEXA). The secondary objective is to gather high quality data to estimate the effect size of 6-months of GHRT versus placebo on 1) cardiometabolic risk factors; 2) lean body mass; 3) quality of life; 4) severity of fatigue symptoms; 5) severity of depression, anxiety, and stress symptoms; and 6) pain severity and pain interference.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Gulf War Syndrome, Adult Growth Hormone Deficiency

Keywords

recombinant human growth hormone, growth hormone replacement therapy

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

This is a phase II, randomized, double-blind, placebo-controlled, futility trial.

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

36 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Growth Hormone Replacement Therapy

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Recombinant human growth hormone

Other Intervention Name(s)

Somatropin

Intervention Description

recombinant human growth hormone (rhGH)

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

placebo

Primary Outcome Measure Information:

Title

Change in truncal fat mass from baseline to six months

Description

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Cardiometabolic Risk Factors

Description

Time Frame

6 months

Title

Lean body mass

Description

Time Frame

6 months

Title

Assessment of quality of life

Description

Time Frame

6 months

Title

Fatigue

Description

Fatigue will be measured using the Fatigue Severity Scale. The questionnaire minimum score is a 9 and maximum score is 63. Higher scores represent greater fatigue severity.

Time Frame

6 months

Title

Depression, Anxiety, and Stress

Description

Time Frame

6 months

Title

Pain Intensity and Interference

Description

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

64 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Being a veteran of the Gulf War conflict with a history of deployment to Operation Desert Storm or Desert Shield between 1990-91 age less than or equal to 64 years old have a diagnosis of Gulf War Illness assessed by study investigators have adult growth hormone deficiency diagnosed by glucagon stimulation test (cut point 3.0 mcg/L if BMI is less than or equal to 25 or 1.0 mcg/L if BMI is greater than 25) 4-week stability on any psychotropic medications 3-month stability on all hormone treatments able and willing to provide informed consent to participant in the study and complete study protocol Exclusion Criteria: history of a psychiatric disorder with substantial impact on functional status or quality of life (e.g., schizophrenia, schizoaffective disorder, bipolar, or other psychotic disorder) history of neurologic disorder other than traumatic brain injury with substantial impact on the quality of life other known cause for growth hormone deficiency (GHD) including history of childhood onset GHD, hypothalamic/pituitary disease, history of brain radiation, or genetic mutations known to lead to GHD active suicidal ideation as determined by a score of 2 points or higher on the Columbia Suicide Severity Rating Scale suicidal behavior in the past 6 months contraindication to recombinant human growth hormone (rhGH) such as hypersensitivity to rhGH or any of the components of the supplied product acute medical illness, active infection, cancer, or decompensated chronic medical illness (e.g., decompensated diabetes mellitus, congestive heart failure, chronic obstructive pulmonary disease) evidence of substance use disorder in the past 6 months other than mild alcohol or cannabis use disorder diagnosed by clinician at time of screening. urine toxicology evidence of illicit drug use (excluding cannabis) within the past 90 days prior to screening BMI > 35 or body weight > 350 lbs abnormal pituitary anatomy documented by an MRI using a Sella protocol women who are pregnant or of child-bearing potential who are unable/unwilling to use one of the following barrier contraceptives: condoms, diaphragm, cervical cap, or intrauterine device current use of the following: growth hormone, estrogen or estrogen-like dietary supplements, hormonal contraceptives, progestin, insulin growth factor 1 (IGF-1), or chronic glucocorticoid use in supraphysiologic doses 15) currently enrolled in any other interventional drug trials unless prior approval is provided by the study chairs and the study sponsor

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Audri Villalon, BS

Phone

(713) 794-8517

audriv@bcm.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Ricardo Jorge, MD

Organizational Affiliation

Baylor College of Medicine

Official's Role

Principal Investigator

Facility Information:

Facility Name

Michael E. DeBakey VA Medical Center

City

Houston

State/Province

Texas

ZIP/Postal Code

77030

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Dakota Broadway

dakota.broadway@bcm.edu

First Name & Middle Initial & Last Name & Degree

Ricardo Jorge, MD

Facility Name

VA Puget Sound Healthcare System

City

Seattle

State/Province

Washington

ZIP/Postal Code

98108

Country

United States

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Megan Herodes, BS

megan.herodes@va.gov

First Name & Middle Initial & Last Name & Degree

Jose M Garcia, MD

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

The data supporting the findings in this study may be made available upon request to VA and non-VA researchers in accordance to VA policy.

IPD Sharing Time Frame

Data will be available up to 24 months after article publication.

IPD Sharing Access Criteria

Access to trial data can be requested by qualified researchers engaging in independent scientific research and will be provided following the review and approval of a research proposal, statistical analysis plan, and data usage agreement.

Learn more about this trial

Growth Hormone Replacement in Veterans With GWI and AGHD (GWIT)

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