Phase 2 Completed N=44 Randomized Treatment

Telmisartan to Reduce AIDS-Related Fibrotic and Inflammatory Contributors (TRAFIC Study)

Source: ClinicalTrials.gov NCT01928927 ↗

Enrolled (actual)

Serious AEs

9.1%

Results posted

Apr 2017

Primary outcomePrimary: Change in Percent Collagen I Deposition on Lymph Node Pathology From Baseline to Week 48 — -2.44; -6.08 percent area stain positive — p=0.97

Summary

The main goal of this study was to see if a drug called telmisartan would decrease fibrosis (scarring) and inflammation (irritation) in people who are infected with HIV and doing well on their HIV medications. The study was also done to see what effects telmisartan has on other signs of disease and inflammation in the body, and to see whether people who have HIV can take telmisartan safely and without side effects that make them want to stop the drug. Telmisartan is FDA-approved for treating high blood pressure and decreasing the chance of heart attacks and strokes in people over the age of 55 years of age who are at high risk for these events.

Outcome Measures

Outcome	Result	p-value
PRIMARY Change in Percent Collagen I Deposition on Lymph Node Pathology From Baseline to Week 48	-2.44; -6.08	0.97
PRIMARY Change in Percent Collagen I Deposition on Subcutaneous Abdominal Adipose Tissue Pathology From Baseline to Week 48	-1.43; 0.36	0.61
SECONDARY Change in Percent Fibronectin Deposition on Lymph Node Pathology From Baseline to Week 48	0.01; 0.61	—
SECONDARY Change in Percent Fibronectin Deposition on Subcutaneous Abdominal Adipose Tissue Pathology From Baseline to Week 48	-0.82; -4.01	—
SECONDARY Change in Percent Collagen VI Deposition on Subcutaneous Abdominal Adipose Tissue Pathology From Baseline to Week 48	-0.41; -1.36	—
SECONDARY Highest Grade Non-biopsy-related Adverse Event	12; 6; 0; 0; 11; 3	—
SECONDARY Change in IL-6 From Baseline to Week 4	-0.50; -0.01	—
SECONDARY Change in IL-6 From Baseline to Week 24	-0.53; 0.04	—
SECONDARY Change in IL-6 From Baseline to Week 48	-0.46; -0.03	—
SECONDARY Change in IL-7 From Baseline to Week 4	0.48; -0.32	—
SECONDARY Change in IL-7 From Baseline to Week 24	0.51; -1.36	—
SECONDARY Change in IL-7 From Baseline to Week 48	0.06; 0.53	—
SECONDARY Change in Adiponectin From Baseline to Week 4	177.20; 161.00	—
SECONDARY Change in Adiponectin From Baseline to Week 24	-582; 1222.60	—
SECONDARY Change in Adiponectin From Baseline to Week 48	-138.70; 113.80	—
SECONDARY Change in Collagen I C-terminal Pro-peptide (CICP) From Baseline to Week 4	-2.14; -9.10	—
SECONDARY Change in Collagen I C-terminal Pro-peptide (CICP) From Baseline to Week 24	-13.78; -1.17	—
SECONDARY Change in Collagen I C-terminal Pro-peptide (CICP) From Baseline to Week 48	-10.76; -6.10	—
SECONDARY Change in Hyaluronic Acid From Baseline to Week 4	-0.03; 3.14	—
SECONDARY Change in Hyaluronic Acid From Baseline to Week 24	-1.62; 3.71	—
SECONDARY Change in Hyaluronic Acid From Baseline to Week 48	-2.74; -1.79	—
SECONDARY Change in sCD14 From Baseline to Week 4	-0.03; 0.05	—
SECONDARY Change in sCD14 From Baseline to Week 24	0.06; -0.08	—
SECONDARY Change in sCD14 From Baseline to Week 48	-0.08; 0	—
SECONDARY Change in sCD163 From Baseline to Week 4	34.08; 0.88	—
SECONDARY Change in sCD163 From Baseline to Week 24	58.72; 9.58	—
SECONDARY Change in sCD163 From Baseline to Week 48	31.14; 5.32	—
SECONDARY Change in TGF-β1 From Baseline to Week 4	793.37; -1074.87	—
SECONDARY Change in TGF-β1 From Baseline to Week 24	175.02; 678.43	—
SECONDARY Change in TGF-β1 From Baseline to Week 48	-319.17; -516.45	—
SECONDARY Change in TGF-β2 From Baseline to Week 4	70.74; -129.40	—
SECONDARY Change in TGF-β2 From Baseline to Week 24	75.84; -134.68	—
SECONDARY Change in TGF-β2 From Baseline to Week 48	44.45; -55.94	—
SECONDARY Change in TGF-β3 From Baseline to Week 4	31.26; -95.17	—
SECONDARY Change in TGF-β3 From Baseline to Week 24	34.64; -68.01	—
SECONDARY Change in TGF-β3 From Baseline to Week 48	-0.47; -55.21	—
SECONDARY Change in Circulating CD4+ T Cell Count From Baseline to Week 12	-17.50; 59.50	—
SECONDARY Change in Circulating CD4+ T Cell Count From Baseline to Week 24	13; 61.5	—
SECONDARY Change in Circulating CD4+ T Cell Count From Baseline to Week 48	9; 97	—
SECONDARY Change in Circulating CD8+ T Cell Count From Baseline to Week 12	-33.5; 83	—
SECONDARY Change in Circulating CD8+ T Cell Count From Baseline to Week 24	-3.5; 80.5	—
SECONDARY Change in Circulating CD8+ T Cell Count From Baseline to Week 48	10; 97	—
SECONDARY Change in Fasting Glucose From Baseline to Week 48	4; 2	—
SECONDARY Change in Fasting HDL Cholesterol From Baseline to Week 48	-1; -4	—
SECONDARY Change in Fasting Insulin From Baseline to Week 48	3; 0	—
SECONDARY Change in Fasting LDL Cholesterol From Baseline to Week 48	-12; -7.4	—
SECONDARY Change in Fasting Total Cholesterol From Baseline to Week 48	-8; -2	—
SECONDARY Change in Fasting Triglycerides From Baseline to Week 48	7; -16	—
SECONDARY Change in HOMA-IR From Baseline to Week 48	0.76; -0.04	—
SECONDARY Prevalence of Metabolic Syndrome at Week 24.	6; 1; 15; 10	—
SECONDARY Presence of Metabolic Syndrome at Week 48.	7; 0; 14; 13	—
SECONDARY Change in Waist Circumference From Baseline to Week 24	0.90; 0.57	—
SECONDARY Change in Waist Circumference From Baseline to Week 48	0.77; -0.08	—
SECONDARY Change in Waist-to-hip Ratio From Baseline to Week 24	0; 0.01	—
SECONDARY Change in Waist-to-hip Ratio From Baseline to Week 48	0; 0.02	—
SECONDARY Change in Expression of CD38+HLA-DR+ on CD4+ From Baseline to Week 24	0.20; -1.35	—
SECONDARY Change in Expression of CD38+HLA-DR+ on CD8+ From Baseline to Week 24	0.60; -0.95	—
SECONDARY Change in Expression of CD38+HLA-DR+ on CD4+ From Baseline to Week 48	-0.30; -0.60	—
SECONDARY Change in Expression of CD38+HLA-DR+ on CD8+ From Baseline to Week 48	-0.40; -0.20	—
SECONDARY Change in Expression of CD163+ in Adipose Tissue From Baseline to Week 48	-0.19; 0.87	—
SECONDARY Change in Expression of CD4+ in Lymphoid Tissue From Baseline to Week 48.	1; -7.8	—
SECONDARY Change in Expression of CD8+ in Lymphoid Tissue From Baseline to Week 48.	-1.19; 3.9	—
SECONDARY Change in Expression of CD163+ in Lymphoid Tissue From Baseline to Week 48.	-0.13; 0.15	—
SECONDARY Change in Expression of CD68+ in Lymphoid Tissue From Baseline to Week 48.	-0.02; 0.08	—
SECONDARY Change in Expression of CD38+HLA-DR+ on CD4+ in Lymphoid Tissue From Baseline to Week 48.	-0.33; 0.06	—
SECONDARY Change in Expression of CD38+HLA-DR+ on CD8+ in Lymphoid Tissue From Baseline to Week 48.	0.13; -0.22	—

Eligibility Criteria

Step 1 Inclusion Criteria:

HIV-1 infection, documented by any licensed rapid HIV test or HIV enzyme or chemiluminescence immunoassay (E/CIA) test kit at any time prior to Step 1 entry and confirmed by a licensed Western blot or a second antibody test by a method other than the initial rapid HIV and/or E/CIA, or by HIV-1 antigen, or plasma HIV-1 RNA viral load >2000 copies/mL on two occasions.
On antiretroviral therapy (ART) continuously for ≥48 weeks prior to Step 1 entry.
Documentation of HIV-1 RNA 200 copies/mL in the 48 weeks prior to Step 1 entry.
One HIV-1 RNA 200-500 copies/mL in the 24 weeks prior to Step 1 entry that is not immediately preceded and followed by HIV-1 RNA 24 weeks prior to Step 1 entry.
Confirmed systolic blood pressure >160 mmHg or 100 mmHg.
Known untreated renal artery stenosis.
Known cirrhosis or severe liver disease (eg, ascites, encephalopathy, history of variceal bleeding).

NOTE: Potential subjects with chronic hepatitis B or C virus infection with no known cirrhosis or severe liver disease may participate in the study, provided there are no plans to start therapy for hepatitis C infection during the 48-week study duration.

Unstable coronary artery disease/angina or decompensated congestive heart failure.
Either breastfeeding or pregnant within 24 weeks prior to Step 1 entry.
Use of thiazolidinediones or any angiotensin receptor blocker (ARB) or angiotensin converting enzyme inhibitor (ACEi) in the 24 weeks prior to Step 1 entry. If the subject took either of these classes of medications for less than 2 weeks in the 24 weeks prior to Step 1 entry, the subject may enroll if 30 days have passed since the last dose. If the subject is diabetic and/or has a calculated glomerular filtration rate (GFR) /=3x ULN (upper limit of normal)
Alanine aminotransferase (ALT) (SGPT) >/=3x ULN
Partial thromboplastin time (PTT) >1.2x ULN
Prothrombin time (PT) >1.2x ULN
Heritable connective tissue disorders (eg Ehlers-Danlos syndrome, osteogenesis imperfecta, Stickler syndrome, Marfan's syndrome).

NOTE: Subjects with acquired/autoimmune chronic inflammatory diseases/connective tissue disorders who are clinically stable (in the opinion of the site investigator) and not on a prohibited medication may enroll with approval of the A5317 study chairs.

Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to Step 1 entry.
Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
Any condition that, in the opinion of the site investigator, would compromise the subject's ability to participate in the study.

Step 2 Exclusion Criteria:

Any AE associated with the Step 1 entry biopsy that would exclude the subject from undergoing follow-up biopsy at week 48.

View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT01928927). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.