Metabolic and QOL Effects of GH Treatment in Patients With TBI and AGHD

Growth hormone replacement has consistently shown improvements in body composition, exercise
capacity, endothelial function, inflammatory biomarkers, bone mineral density, lipoprotein
metabolism, and self-reported quality of Life (QOL) in patients suffering from adult growth
hormone deficiency (AGHD). One of the causes for AGHD is traumatic brain injury (TBI), a
condition that affects approximately 20% of Veterans from Operation Enduring Freedom (OEF),
Operation Iraqi Freedom (OIF), and Operation New Dawn (OND). Because OIF/OEF/OND Veterans are
a new population, there is a paucity of data regarding the effects of rhGH in these patients.
The investigators propose to perform a pilot observational study of Veterans with confirmed
adult growth hormone deficiency (AGHD) due to TBI who have been prescribed recombinant human
growth hormone (rhGH) replacement in order to determine changes in metabolic parameters and
QOL induced by rhGH.

Our hypothesis is that GH replacement will improve QOL and metabolic parameters (glucose,
insulin resistance, lipids, inflammatory markers, and body composition) in patients with
confirmed AGHD due to TBI.The primary aim for this proposal is to determine the effects of
rhGH treatment given daily for 6 months to Veterans with TBI and AGHD on QoL measured by the
Quality of Life Assessment for GHD in Adults questionnaire (QoL-AGHDA, primary outcome).
Secondary specific aims for this proposal are to gather high quality pilot data of the
effects of 6 months of rhGH replacement in Veterans with TBI and AGHD.

Inclusion Criteria:

1. OEF/OIF/OND deployment confirmed by available records

2. history of combat exposure during deployment as determined by a score greater than 1
on the Combat Experiences sub-scale of the Deployment Risk and Resilience Inventory-2
(DRRI-2)

3. age >18 years

4. a history of TBI defined according to the DoD/VA guidelines and characterized by the
Ohio State TBI Inventory

5. history of AGH deficiency diagnosed by: a) a GH stimulatory test; or b) low plasma
IGF-1 level and 3 pituitary hormone deficiencies

6. have been prescribed rhGH replacement by a clinical provider

7. If the Veteran is receiving psychotropic medications he should be on stable doses for
at least 4 weeks before their enrollment in the study.

Exclusion Criteria:

1. Other untreated pituitary deficiencies [patients with other hormone deficiencies will
have to be on stable replacement for at least three months before including them on
the study; two months of stable replacement is required for hydrocortisone therapy for
adrenal insufficiency]

2. tumors, or other causes of AGHD (e.g. childhood onset GHD, pituitary surgery, tumors,
radiation)

3. history of neurologic or psychiatric disorder such as stroke, spinal cord injury,
bipolar disorder, or schizophrenia that has a significant impact in the Veteran's
functional status and QoL

4. contraindication to rhGH therapy (e.g. hypersensitivity to rhGH or any of the
components of the supplied product, including metacresol, glycerin, or benzyl alcohol)

5. acute medical illness, active infection, neoplastic disease or decompensated chronic
medical illness such as diabetes mellitus (A1c >9%), congestive heart failure or
chronic obstructive pulmonary disease

6. evidence of alcohol dependence, alcohol abuse or drug use disorder during the three
months previous to enrollment in the study

7. evidence of inadequate levels of effort in performing neuropsychological tests as
suggested by scoring less than 41 on Trial I of the Test of Memory and Malingering
(TOMM)

8. due to the decreased specificity of the AGHD diagnostic tests in this setting and
weight/size limitations of the DEXA scanner, we will exclude morbid obese subjects
defined as having a BMI greater than 35 or body weight > 350 lbs

9. use of rhGH in the previous 6 months

10. active or recent (6 months) history of coronary artery or cerebrovascular disease