Clinical trial NCT01591902: Diabetic Retinopathy in HIV Subjects Treated With EGRIFTA®
Official title: A Prospective, Randomized, Placebo-controlled, Double-blind Clinical Trial to Evaluate Whether EGRIFTA® (Tesamorelin for Injection), 2 mg Once Daily SC, Increases the Risk of Development or Progression of Diabetic Retinopathy When Administered to HIV-infected Subjects With Abdominal Lipohypertrophy and Concomitant Diabetes
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Diabetic Retinopathy
HIV
Lead sponsor: Theratechnologies
Sponsor class: INDUSTRY
First posted: 2012-05-04
Enrollment: 129
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: To show the non-inferiority of EGRIFTA® vs. placebo in the development or progression of Diabetic Retinopathy in HIV-infected subjects with concomitant abdominal lipohypertrophy and Type 2 diabetes mellitus (T2DM).

Detailed description: To date, EGRIFTA® has not been studied for longer than 1 year in human subjects, nor has EGRIFTA® been studied in Type 2 diabetic HIV-infected subjects who are receiving oral hypoglycemic agents, GLP-1 analogues, or insulin. The present study will assess the potential of EGRIFTA® to induce or exacerbate DR in HIV-infected subjects on antiretroviral therapy who have concomitant abdominal lipohypertrophy and T2DM, and explore the long-term effects of EGRIFTA® on glycemic control and major adverse cardiovascular event (MACE) in this population.

Eligibility criteria: Inclusion criteria:

1. Subject has given written informed consent and is willing to comply with the requirements of the protocol;
2. Subject is an adult man or woman (≥ 18 years old);
3. Subject has laboratory confirmed HIV infection;
4. Subject is receiving ART that has been stable for at least 8 weeks prior to screening;
5. Subject has physical evidence of abdominal lipohypertrophy, as determined by the examining study physician;
6. Subject has T2DM as determined by previous HbA1c ≥ 6.5%, previous fasting plasma glucose

   * ≥ 126 mg/dL (7.0 mmol/L), and/or previous 2-hour plasma glucose ≥ 200 mg/dL (11.1 mmol/L) during oral glucose tolerance testing (OGTT), and/or previous random plasma glucose ≥ 200 mg/dL (11.1 mmol/L) with symptoms of uncontrolled DM;
   * if subject has been diagnosed with T2DM and is on glucose lowering medications for greater than 1 year the above glucose parameters do not apply;
7. Subject, at the time of screening, has HbA1c between 6.0% and 12.0%;
8. Subject's diabetes has been treated for at least 1 year by diet alone, individuals who are on a stable dose (at least 3 months) of insulin, an OHA, or a GLP-1 analogue plus insulin to control diabetes are permitted if their HbA1C is below 6.0%. OHA, GLP-1 analogue, or OHA/GLP-1 analogue plus insulin according to current American Diabetes Association (ADA) guidelines, and doses have been stable for at least 3 months;
9. If the subject is using lipid lowering drugs, the dose must be stable for at least 2 months prior to screening;
10. Subject must have an electrocardiogram (ECG) without clinically significant abnormalities within 6 months prior to screening;
11. Pre-menopausal women of childbearing potential are eligible only if they are not pregnant (negative urine pregnancy tests at screening and baseline) or lactating and are using an acceptable form of birth control prior to study entry and for at least 2 months after completing treatment. Acceptable contraception is defined as two barrier methods, or one barrier method with a spermicide, or an intrauterine device, or an oral contraceptive;
12. Women of non-childbearing potential must be post-menopausal (no menses for more than 1 year) or surgically sterile (tubal ligation or hysterectomy);
13. Women over 40 years old must have a negative mammogram within 6 months prior to screening or a mammogram will be taken at screening;
14. Men must have a normal prostate exam and a prostate specific antigen (PSA) Individuals who are on a stable dose (at least 3 months) of insulin, less than or equal to 5 ng/mL within 6 months prior to screening or PSA and, for men 50 years of age or older, a prostate specific antigen will be measured at screening

Exclusion Criteria:

1. Subject has Type 1 DM;
2. Subject has body mass index (BMI) \< 18.5 kg.m2;
3. Subject has or has had an opportunistic infection or acquired immune deficiency syndrome (AIDS)-defining illness within 3 months of screening;
4. Subject has or has had a malignancy or, for women, personal or family (first degree relative) history of breast cancer. Exceptions are basal cell carcinoma, in situ carcinoma of the cervix, in situ anal carcinoma, treated and stable cutaneous squamous cell carcinoma. and stable Kaposi's sarcoma;
5. Pre-existing PDR or severe non-PDR (NPDR), defined as an ETDRS level of ≥ 53 in either eye;
6. Subject has or has had cytomegalovirus (CMV) retinitis, toxoplasmosis, or any other ocular infection that would prevent evaluation of DR;
7. Subject has previously been treated for DR (treatments such as laser photocoagulation, intravitreal injection, or vitrectomy);
8. Subject has any of the following illnesses or conditions:

   1. hypopituitarism, history of pituitary tumor or pituitary surgery;
   2. untreated hypothyroidism;
   3. head irradiation or head trauma that has affected the somatotropic axis;
   4. uncontrolled hypertension, defined as systolic pressure \> 140 mm Hg and diastolic pressure \> 90 mm Hg;
   5. unstable CV condition, defined as:

   i. acute MI; ii. unstable angina; iii. decompensated congestive heart failure (CHF, new onset or exacerbation); iv. stroke; v. history of any of the above within 6 months prior to screening; f. hepatic abnormality, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \> 3 times the upper limit of normal (3 x ULN); g. renal abnormality, defined as serum creatinine \> 2 x ULN; h. lipid metabolism abnormality, defined as fasting triglycerides \> 1500 mg/dL; i. anemia, defined as hemoglobin ≤ 7 g/dL;
9. Drug or hormone use as follows

   1. Men: change in regimen or supraphysiological dose of testosterone within 2 months prior to screening;
   2. anabolic steroids, GH, GH secretagogue, GHRF products or analogs (including EGRIFTA®), IGF-1, or IGF binding protein 3 (IGFBP 3) within 6 months prior to screening;
10. Drug or alcohol dependence within 6 months prior to screening;
11. Subject is using or has used anorectics, anorexigenics, or anti-obesity agents within 3 months prior to screening;
12. Subject is pregnant or nursing;
13. Other significant disease that, in the Investigator's opinion, would exclude the subject from the trial;
14. Participation, within 30 days prior to screening, in another clinical trial of an investigational agent that could affect IGF-1 levels;
15. Known hypersensitivity to the study drug treatments.

Primary outcomes:
measure: Difference in percentages of subjects with a 3-step or greater progression (from both eyes) on the Early Treatment Diabetic Retinopathy Study (ETDRS) PERSON scale.
timeFrame: 3 years
Secondary outcomes:
measure: Change from baseline in HbA1c by intensification of concomitant diabetic treatment
timeFrame: 3 years
Other outcomes:
Locations:
city: Phoenix
country: United States
facility: Southwest Center for HIV/AIDS
state: Arizona
city: Phoenix
country: United States
facility: Spectrum Medical Group
state: Arizona
city: Los Angeles
country: United States
facility: 5P21 Rand Schrader Clinic
state: California
city: Los Angeles
country: United States
facility: University of California CARE Clinic, Los Angeles
state: California
city: Palm Springs
country: United States
facility: Palmtree Clinical Research, Inc.
state: California
city: San Diego
country: United States
facility: UCSD Antiviral Research Center
state: California
city: San Francisco
country: United States
facility: VAMC, Infectious Disease Section 111W
state: California
city: Washington
country: United States
facility: Capital Medical Associates, PC
state: District of Columbia
city: Fort Lauderdale
country: United States
facility: Gary J. Richmond, M.D., PA
state: Florida
city: Orlando
country: United States
facility: Orange County Health Department
state: Florida
city: West Palm Beach
country: United States
facility: Triple O Research Institute
state: Florida
city: Wilton Manors
country: United States
facility: Rowan Tree Medical , P.A.
state: Florida
city: Berkley
country: United States
facility: Be Well Medical Center, P.C.
state: Michigan
city: Saint Louis
country: United States
facility: Southampton Clinical Research, Inc d.b.a. Central West Clinical Research
state: Missouri
city: Saint Louis
country: United States
facility: Southampton Healthcare, Inc.
state: Missouri
city: Somers Point
country: United States
facility: South Jersey Infectious Disease
state: New Jersey
city: Oklahoma City
country: United States
facility: Harold Hamm Diabetes Center at the University of Oklahoma
state: Oklahoma
city: Portland
country: United States
facility: Fanno Creek Clinic, LLC
state: Oregon
city: Austin
country: United States
facility: Central Texas Clinical Research
state: Texas
city: Bellaire
country: United States
facility: St. Hope Foundation, Inc.
state: Texas
city: Dallas
country: United States
facility: Dallas VA Medical Center
state: Texas
city: Dallas
country: United States
facility: UT Southwestern Medical Center, Atten: HIV Research Unit
state: Texas
city: Houston
country: United States
facility: Research Access Network
state: Texas
city: Seattle
country: United States
facility: Virginia Mason Medical Center
state: Washington
Study officials:
name: Marilyn De Chantal
References: